Publications by authors named "Gert J de Borst"

209 Publications

External Validation of Risk Prediction Models to Improve Selection of Patients for Carotid Endarterectomy.

Stroke 2021 Oct 12:STROKEAHA120032527. Epub 2021 Oct 12.

Department of Vascular Surgery, University Medical Center Utrecht, the Netherlands. (G.J.d.B).

Background And Purpose: The net benefit of carotid endarterectomy (CEA) is determined partly by the risk of procedural stroke or death. Current guidelines recommend CEA if 30-day risks are <6% for symptomatic stenosis and <3% for asymptomatic stenosis. We aimed to identify prediction models for procedural stroke or death after CEA and to externally validate these models in a large registry of patients from the United States.

Methods: We conducted a systematic search in MEDLINE and EMBASE for prediction models of procedural outcomes after CEA. We validated these models with data from patients who underwent CEA in the American College of Surgeons National Surgical Quality Improvement Program (2011-2017). We assessed discrimination using C statistics and calibration graphically. We determined the number of patients with predicted risks that exceeded recommended thresholds of procedural risks to perform CEA.

Results: After screening 788 reports, 15 studies describing 17 prediction models were included. Nine were developed in populations including both asymptomatic and symptomatic patients, 2 in symptomatic and 5 in asymptomatic populations. In the external validation cohort of 26 293 patients who underwent CEA, 702 (2.7%) developed a stroke or died within 30-days. C statistics varied between 0.52 and 0.64 using all patients, between 0.51 and 0.59 using symptomatic patients, and between 0.49 to 0.58 using asymptomatic patients. The Ontario Carotid Endarterectomy Registry model that included symptomatic status, diabetes, heart failure, and contralateral occlusion as predictors, had C statistic of 0.64 and the best concordance between predicted and observed risks. This model identified 4.5% of symptomatic and 2.1% of asymptomatic patients with procedural risks that exceeded recommended thresholds.

Conclusions: Of the 17 externally validated prediction models, the Ontario Carotid Endarterectomy Registry risk model had most reliable predictions of procedural stroke or death after CEA and can inform patients about procedural hazards and help focus CEA toward patients who would benefit most from it.
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http://dx.doi.org/10.1161/STROKEAHA.120.032527DOI Listing
October 2021

Defining the awake baseline blood pressure in patients undergoing carotid endarterectomy.

Int Angiol 2021 Sep 22. Epub 2021 Sep 22.

Department of Vascular Surgery, G04.129, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands -

Background: To minimize the incidence of intraoperative stroke following carotid endarterectomy (CEA) under general anaesthesia, blood pressure (BP) is suggested to be maintained between 'awake baseline' BP and 20% above. However, there is neither a widely accepted protocol nor a definition to determine this awake BP. In this study, we analysed the BP during hospital admission in the days before CEA and propose a definition of how to determine awake BP.

Methods: In our cohort of 1180 CEA-patients, all non-invasive BP-measurements were retrospectively analysed. BP was measured during preoperative outpatient screening (POS), the last three days before surgery at the ward and in the operating room(OR) directly before anaesthesia. Primary outcome was the comparability of all these preoperative BP measurements. Secondary outcome was the comparability of preoperative BP measurements stratified for postoperative stroke within 30 days.

Results: POS BP [148±22/80±12mmHg(mean arterial pressure(MAP)103±14mmHg)] and the BP measured on the ward 3,2,1 days before surgery and on the day of surgery [146±25/77±13(MAP 100±15)], [142±23/76±13(MAP 98±15)], [145±23/76±12(MAP 99±14)] and [144±22/75±12mmHg(MAP 98±14)] were comparable (all p=NS). However, BP in the OR directly before anaesthesia was higher, [163±27/88±15mmHg(MAP 117±18mmHg)] (p<0.01 vs all other preoperative moments). A significant higher pre-induction systolic BP and MAP was observed in patients suffering a stroke within 30-days compared to patients without (p=0.03 and 0.04 respectively).

Conclusions: Awake BP should be determined by averaging available BP-values collected preoperatively on the ward and POS. BP measured in the OR directly before induction of anaesthesia overestimates 'awake' BP and should therefore not be used.
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http://dx.doi.org/10.23736/S0392-9590.21.04679-4DOI Listing
September 2021

A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease.

Ann Transl Med 2021 Aug;9(15):1260

Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Objective: In this narrative review, we aim to review imaging biomarkers that carry the potential to non-invasively guide stroke risk stratification for treatment optimization.

Background: Carotid atherosclerosis plays a fundamental part in the occurrence of ischemic stroke. International guidelines select the optimal treatment strategy still mainly based on the presence of clinical symptoms and the degree of stenosis for stroke prevention in patients with atherosclerotic carotid plaques. These guidelines, based on randomized controlled trials that were conducted three decades ago, recommend carotid revascularization in symptomatic patients with high degree of stenosis versus a conservative approach for most asymptomatic patients. Due to optimization of best medical therapy and risk factor control, it is suggested that a subgroup of symptomatic patients is at lower risk of stroke and may not benefit from revascularization, whereas a selective subgroup of high-risk asymptomatic patients would benefit from this procedure.

Methods: A literature search was performed for articles published up to December 2020 using PubMed, EMBASE and Scopus. Based on the literature found, change in stenosis degree and volume, plaque echolucency, plaque surface, intraplaque haemorrhage, lipid-rich necrotic core, thin fibrous cap, inflammation, neovascularization, microembolic signals, cerebrovascular reserve, intracranial collaterals, silent brain infarcts, diffusion weighted imaging lesions and white matters lesions have the potential to predict stroke risk.

Conclusions: The applicability of imaging biomarkers needs to be further improved before the potential synergistic prognostic ability of imaging biomarkers can be verified on top of the clinical biomarkers. In the future, the routine and combined assessment of both plaque and brain imaging biomarkers might help to improve optimization of treatment strategies in individual patients with atherosclerotic carotid artery disease.
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http://dx.doi.org/10.21037/atm-21-1166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421959PMC
August 2021

Mast Cell Distribution in Human Carotid Atherosclerotic Plaque Differs Significantly by Histological Segment.

Eur J Vasc Endovasc Surg 2021 Sep 13. Epub 2021 Sep 13.

Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Objective: Mast cells (MCs) are important contributors to atherosclerotic plaque progression. For prospective studies on mast cell contributions to plaque instability, the distribution of intraplaque MCs needs to be elucidated. Plaque stability is generally histologically assessed by dividing the plaque specimen into segments to be scored on an ordinal scale. However, owing to competitive use, studies may have to deviate to adjacent segments, yet intersegment differences of plaque characteristics, especially MCs, are largely unknown. Therefore, the hypothesis that there is no segment to segment difference in MC distribution between atherosclerotic plaque segments was tested, and intersegment associations between MCs and other plaque characteristics was investigated.

Methods: Twenty-six carotid atherosclerotic plaques from patients undergoing carotid endarterectomy included in the Athero-Express Biobank were analysed. The plaque was divided in 5 mm segments, differentiating between the culprit lesion (segment 0), adjacent segments (-1/+1) and more distant segments (-2/+2) for the presence of MCs. The associations between the intersegment distribution of MCs and smooth muscle cells, macrophage content, and microvessel density in the culprit lesion were studied.

Results: A statistically significant difference in MCs/mm between the different plaque segments (p < .001) was found, with a median of 2.79 (interquartile range [IQR] 1.63 - 7.10) for the culprit lesion, 1.34 (IQR 0.26 - 4.45) for the adjacent segment, and 0.62 (0.14 - 2.07) for the more distant segment. Post hoc analyses showed that intersegment differences were due to differences in MCs/mm between the culprit and adjacent segment (p = .037) and between the culprit lesion and the more distant segment (p < .001). MCs/mm in multiple different segments were positively correlated with microvessel density and macrophage content in the culprit lesion.

Conclusion: MC numbers reveal significant intersegment differences in human carotid plaques. Future histological studies on MCs should use a standardised segment for plaque characterisation as plaque segments cannot be used interchangeably for histological MC analyses.
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http://dx.doi.org/10.1016/j.ejvs.2021.07.008DOI Listing
September 2021

Pre-Operative Plasma Extracellular Vesicle Proteins are Associated with a High Risk of Long Term Secondary Major Cardiovascular Events in Patients Undergoing Carotid Endarterectomy.

Eur J Vasc Endovasc Surg 2021 Sep 9. Epub 2021 Sep 9.

Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Objective: Patients undergoing carotid endarterectomy (CEA) maintain a substantial residual risk of major cardiovascular events (MACE). Improved risk stratification is warranted to select high risk patients qualifying for secondary add on therapy. Plasma extracellular vesicles (EVs) are involved in atherothrombotic processes and their content has been related to the presence and recurrence of cardiovascular events. The association between pre-operative levels of five cardiovascular disease related proteins in plasma EVs and the post-operative risk of MACE was assessed.

Methods: In 864 patients undergoing CEA from 2002 to 2016 included in the Athero-Express biobank, three plasma EV subfractions (low density lipoprotein [LDL], high density lipoprotein [HDL], and tiny extracellular vesicles [TEX]) were isolated from pre-operative blood samples. Using an electrochemiluminescence immunoassay, five proteins were quantified in each EV subfraction: cystatin C, serpin C1, serpin G1, serpin F2, and CD14. The association between EV protein levels and the three year post-operative risk of MACE (any stroke, myocardial infarction, or cardiovascular death) was evaluated using multivariable Cox proportional hazard regression analyses.

Results: During a median follow up of three years (interquartile range 2.2 - 3.0), 137 (16%) patients developed MACE. In the HDL-EV subfraction, increased levels of CD14, cystatin C, serpin F2, and serpin C1 were associated with an increased risk of MACE (adjusted hazard ratios per one standard deviation increase of 1.30, 95% confidence interval [CI] 1.15-1.48; 1.22, 95% CI 1.06-1.42; 1.36, 95% CI 1.16-1.61; and 1.29, 95% CI 1.10-1.51; respectively), independently of cardiovascular risk factors. No significant associations were found for serpin G1. CD14 improved the predictive value of the clinical model encompassing cardiovascular risk factors (net re-classification index = 0.16, 95% CI 0.08-0.21).

Conclusion: EV derived pre-operative plasma levels of cystatin C, serpin C1, CD14, and serpin F2 were independently associated with an increased long term risk of MACE after CEA and are thus markers for residual cardiovascular risk. EV derived CD14 levels could improve the identification of high risk patients who may benefit from secondary preventive add on therapy in order to reduce future risk of MACE.
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http://dx.doi.org/10.1016/j.ejvs.2021.06.039DOI Listing
September 2021

External applicability of SGLT2 inhibitor cardiovascular outcome trials to patients with type 2 diabetes and cardiovascular disease.

Cardiovasc Diabetol 2021 09 8;20(1):181. Epub 2021 Sep 8.

Department of Vascular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Background: Recent treatment guidelines support the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and cardiovascular disease based on the results of cardiovascular outcome trials (CVOTs). Applicability of these trials to everyday patients with type 2 diabetes and cardiovascular disease is however unknown. The aim of this study is to assess the external applicability of SGLT2i CVOTs in daily clinical practice type 2 diabetes patients with established cardiovascular disease.

Methods: Trial in- and exclusion criteria from EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS-CV were applied to 1389 type 2 diabetes patients with cardiovascular disease in the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). To evaluate the difference in cardiovascular risk (MACE) and all-cause mortality between trial eligible and ineligible patients, age and sex-adjusted Cox-regression analyses were performed.

Results: After applying trial in- and exclusion criteria, 48% of UCC-SMART patients with type 2 diabetes and cardiovascular disease would have been eligible for DECLARE-TIMI 58, 35% for CANVAS, 29% for EMPA-REG OUTCOME and 21% for VERTIS-CV. Without the eligibility criteria of HbA, eligibility was 58-88%. For all trials the observed risk for cardiovascular events and all-cause mortality was similar in eligible and ineligible patients after adjustment for age and gender.

Conclusion: A large proportion of patients with type 2 diabetes and cardiovascular disease in daily clinical practice would have been eligible for participation in the SGLT2i CVOTs. Trial eligible and ineligible patients have the same risk for MACE and all-cause mortality.
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http://dx.doi.org/10.1186/s12933-021-01373-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427950PMC
September 2021

Variation in perioperative cerebral and hemodynamic monitoring during carotid endarterectomy.

Ann Vasc Surg 2021 Aug 27. Epub 2021 Aug 27.

Department of Vascular Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Background: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted.

Methods: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres.

Results: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr).

Conclusions: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA.
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http://dx.doi.org/10.1016/j.avsg.2021.06.015DOI Listing
August 2021

Long Term Restenosis Rate After Carotid Endarterectomy: Comparison of Three Surgical Techniques and Intra-Operative Shunt Use.

Eur J Vasc Endovasc Surg 2021 Oct 25;62(4):513-521. Epub 2021 Aug 25.

Department of Neurology and Stroke Centre, University Hospital Basel, University of Basel, Basel, Switzerland.

Objective: Closure of the artery during carotid endarterectomy (CEA) can be done with or without a patch, or performed with the eversion technique, while the use of intra-operative shunts is optional. The influence of these techniques on subsequent restenosis is uncertain. Long term carotid restenosis rates and risk of future ipsilateral stroke with these techniques were compared.

Methods: Patients who underwent CEA in the International Carotid Stenting Study were divided into patch angioplasty, primary closure, or eversion endarterectomy. Intra-operative shunt use was reported. Carotid duplex ultrasound was performed at each follow up. Primary outcomes were restenosis of ≥ 50% and ≥ 70%, and ipsilateral stroke after the procedure to the end of follow up.

Results: In total, 790 CEA patients had restenosis data at one and five years. Altogether, 511 (64.7%) had patch angioplasty, 232 (29.4%) primary closure, and 47 (5.9%) eversion endarterectomy. The cumulative incidence of ≥ 50% restenosis at one year was 18.9%, 26.1%, and 17.7%, respectively, and at five years it was 25.9%, 37.2%, and 30.0%, respectively. There was no difference in risk between the eversion and patch angioplasty group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.45 - 1.81; p = .77). Primary closure had a higher risk of restenosis than patch angioplasty (HR 1.45, 95% CI 1.06 - 1.98; p = .019). The cumulative incidence of ≥ 70% restenosis did not differ between primary closure and patch angioplasty (12.1% vs. 7.1%, HR 1.59, 95% CI 0.88 - 2.89; p = .12) or between patch angioplasty and eversion endarterectomy (4.7%, HR 0.45, 95% CI 0.06 - 3.35; p = .44). There was no effect of shunt use on the cumulative incidence of restenosis. Post-procedural ipsilateral stroke was not more common in either of the surgical techniques or shunt use.

Conclusion: Restenosis was more common after primary closure than conventionally with a patch closure. Shunt use had no effect on restenosis. Patch closure is the treatment of choice to avoid restenosis.
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http://dx.doi.org/10.1016/j.ejvs.2021.06.028DOI Listing
October 2021

The Global Limb Anatomic Staging System (GLASS) for CLTI: Improving Inter-Observer Agreement.

J Clin Med 2021 Aug 4;10(16). Epub 2021 Aug 4.

Department of Vascular Surgery, UCSF Medical Center, San Francisco, CA 94143, USA.

Objective: The 2020 Global Vascular Guidelines aim at improving decision making in Chronic Limb-Threatening Ischemia (CLTI) by providing a framework for evidence-based revascularization. Herein, the Global Limb Anatomic Staging System (GLASS) serves to estimate the chance of success and patency of arterial pathway revascularization based on the extent and distribution of the atherosclerotic lesions. We report the preliminary feasibility results and observer variability of the GLASS. GLASS is a part of the new global guideline and posed as a promising additional tool for EBR strategies to predict the success of lower extremity arterial revascularization. This study reports on the consistency of GLASS scoring to maximize inter-observer agreement and facilitate its application.

Methods: GLASS separately scores the femoropopliteal (FP) and infrapopliteal (IP) segment based on stenosis severity, lesion length and the extent of calcification within the target artery pathway (TAP). In our stepwise approach, we used two angiographic datasets. Each following step was based on the lessons learned from the previous step. The primary outcome was inter-observer agreement measured as Cohen's Kappa, scored by two (step 1 + 2) and four (step 3) blinded and experienced observers, respectively. Steps 1 ( = 139) and 2 ( = 50) were executed within a dataset of a Dutch interventional RCT in CLTI. Step 3 ( = 100) was performed in randomly selected all-comer CLTI patients from two vascular centers in the United States.

Results: In step 1, kappa values were 0.346 (FP) and 0.180 (IP). In step 2, applied in the same dataset, the use of other experienced observers and a provided TAP, resulted in similar low kappa values 0.406 (FP) and 0.089 (IP). Subsequently, in step 3, the formation of an altered stepwise approach using component scoring, such as separate scoring of calcification and adding a ruler to the images resulted in kappa values increasing to 0.796 (FP) and 0.730 (IP).

Conclusion: This retrospective GLASS validation study revealed low inter-observer agreement for unconditioned scoring. A stepwise component scoring provides acceptable agreement and a solid base for further prospective validation studies to investigate how GLASS relates to treatment outcomes.
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http://dx.doi.org/10.3390/jcm10163454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396876PMC
August 2021

Feasibility of Photo-Optical Transcutaneous Oxygen Tension Measurement During Revascularization of the Lower Extremity.

Ann Vasc Surg 2021 Aug 23. Epub 2021 Aug 23.

Department of Vascular and Endovascular Surgery, Jeroen Bosch Ziekenhuis, Netherlands. Electronic address:

Objectives: A novel approach in the evaluation of peripheral arterial disease is the photo-optical oxygen tension measurement (pTCpO2). This modality is suggested to be more practical in use in comparison to standard electro-chemical oxygen tension measurement. Hence, pTCpO2 might be of added value to evaluate revascularization of the lower extremities peri-procedural. We conducted a preliminary feasibility study to analyze the potential of pTCpO2 during revascularization.

Methods: Ten patients scheduled for revascularization of the lower extremities were enrolled. pTCpO2 values of the affected lower extremity were measured pre-operatively, during revascularization and after revascularization. Results were compared to the pre- and postoperative ankle-brachial index (ABI) and to perioperative angiography. Primary endpoint was the feasibility of perioperative pTCpO2 measurement. Secondary endpoints were concordance between pTCpO2, ABI, angiography and clinical outcome.

Results: Two out of twelve measurements were unsuccessful. Eight out of ten patients experienced significant clinical improvement and pTCpO2 increase. Two patients that did not experience clinical improvement corresponded with no changes in intraoperative angiography and without increase in ABI or pTCpO2. A significant and strong correlation was found between prior and after revascularization ABI and pTCpO2 measurements (r = 0.82 P = 0.04).

Conclusions: Photo-optical transcutaneous oxygen tension measurement may serve as an intraoperative tool to evaluate the success of revascularization. pTCpO2 could be an alternative for the ABI to determine the success of lower extremity revascularization.
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http://dx.doi.org/10.1016/j.avsg.2021.05.058DOI Listing
August 2021

Comparison of Photo-optical Transcutaneous Oxygen Tension Measurement with Electro-chemical Transcutaneous Oxygen Tension Measurement in Patients with Arterial Claudication.

Ann Vasc Surg 2021 Aug 17. Epub 2021 Aug 17.

Department of Vascular Surgery, Jeroen Bosch Ziekenhuis,'s-Hertogenbosch, Groningen, The Netherlands.

Purpose: Photo-optical TCpO2 (pTCpO2) has been proposed as a new method to determine the partial oxygen pressure of the lower extremity in patients with peripheral arterial disease. It is aimed to determine the level of agreement between pTCpO2 and the traditional electro-chemical transcutaneous oxygen tension measurement (eTCpO2).

Methods: Eighteen patients with intermittent claudication underwent simultaneous ankle-brachial index measurement, toe-pressure, pTCpO2 and eTCpO2 tests. Oxygen tension levels were measured on anterior chest and calf prior in rest (T0), during induced ischemia (T1) and after blood flow restoration (T2). TCpO2 agreement was assessed according to the principles of Bland and Altman.

Results: Absolute average TCpO2 values differed between eTCpO2 and pTCpO2 for calf in T2 (38,1 mmHg (σ 14,4) vs. 49,8 (σ 22.3) with P = 0.35). The Bland-Altman plots demonstrated eTCpO2 and pTCpO2 bias of 3,7 mmHg (σ 18,8), 11,6 mmHg (σ 17,6) and 6,7 mmHg (σ 23,5) for T0, T1 and T2 for the calf.

Conclusion: pTCpO2 is in agreement with eTCpO2 in measuring pO2 levels of the lower extremity in rest and during induced ischemia in patients with vascular claudication. The large variability between eTCpO2 and pTCpO2 should be accounted for, while pTCpO2 values have a tendency to demonstrate higher values in comparison to eTCpO2.
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http://dx.doi.org/10.1016/j.avsg.2021.05.019DOI Listing
August 2021

European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.

Eur Stroke J 2021 Jun 18;6(2). Epub 2021 Jun 18.

Department for Vascular and Endovascular Surgery, University Hospital, Technical University of Munich (TUM), Munich, Germany.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60-99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70-99% symptomatic stenosis, and we suggest CEA for patients with 50-69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50-99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50-99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.
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http://dx.doi.org/10.1177/23969873211026990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370086PMC
June 2021

European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.

Eur Stroke J 2021 Jun 11;6(2):I-XLVII. Epub 2021 May 11.

Department for Vascular and Endovascular Surgery, University Hospital, Technical University of Munich (TUM), Munich, Germany.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60-99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70-99% symptomatic stenosis, and we suggest CEA for patients with 50-69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50-99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50-99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.
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http://dx.doi.org/10.1177/23969873211012121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370069PMC
June 2021

Clinical Response to Procedural Stroke Following Carotid Endarterectomy: A Delphi Consensus Study.

Eur J Vasc Endovasc Surg 2021 Sep 24;62(3):350-357. Epub 2021 Jul 24.

Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht University, the Netherlands. Electronic address:

Objective: No dedicated studies have been performed on the optimal management of patients with an acute stroke related to carotid intervention nor is there a solid recommendation given in the European Society for Vascular Surgery guideline. By implementation of an international expert Delphi panel, this study aimed to obtain expert consensus on the optimal management of in hospital stroke occurring during or following CEA and to provide a practical treatment decision tree.

Methods: A four round Delphi consensus study was performed including 31 experts. The aim of the first round was to investigate whether the conceptual model indicating the traditional division between intra- and post-procedural stroke in six phases was appropriate, and to identify relevant clinical responses during these six phases. In rounds 2, 3, and 4, the aim was to obtain consensus on the optimal response to stroke in each predefined setting. Consensus was reached in rounds 1, 3, and 4 when ≥ 70% of experts agreed on the preferred clinical response and in round 2 based on a Likert scale when a median of 7 - 9 (most adequate response) was given, IQR ≤ 2.

Results: The experts agreed (> 80%) on the use of the conceptual model. Stroke laterality and type of anaesthesia were included in the treatment algorithm. Consensus was reached in 17 of 21 scenarios (> 80%). Perform diagnostics first for a contralateral stroke in any phase, and for an ipsilateral stroke during cross clamping, or apparent stroke after leaving the operation room. For an ipsilateral stroke during the wake up phase, no formal consensus was achieved, but 65% of the experts would perform diagnostics first. A CT brain combined with a CTA or duplex ultrasound of the carotid arteries should be performed. For an ipsilateral intra-operative stroke after flow restoration, the carotid artery should be re-explored immediately (75%).

Conclusion: In patients having a stroke following carotid endarterectomy, expedited diagnostics should be performed initially in most phases. In patients who experience an ipsilateral intra-operative stroke following carotid clamp release, immediate re-exploration of the index carotid artery is recommended.
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http://dx.doi.org/10.1016/j.ejvs.2021.05.033DOI Listing
September 2021

The US Preventive Services Task Force Recommendation Statement About Screening Asymptomatic Adults for Carotid Stenosis.

JAMA 2021 07;326(1):88-89

University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

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http://dx.doi.org/10.1001/jama.2021.6489DOI Listing
July 2021

Procedural stroke after carotid revascularization: Critical analysis of the literature and standards of reporting.

J Vasc Surg 2021 Jun 26. Epub 2021 Jun 26.

Vascular Surgery Department, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Objective: Mechanisms of procedural stroke after carotid endarterectomy (CEA) or carotid artery stenting are surprisingly underresearched. However, understanding the underlying mechanism could (1) assist in balancing the choice for revascularization vs conservative therapy, (2) assist in choosing either open or endovascular techniques, and (3) assist in taking appropriate periprocedural measures to further decrease procedural stroke rate. The purpose of this study was to overview mechanisms of procedural stroke after carotid revascularization and establish reporting standards to facilitate more granular investigation and individual patient data meta-analysis in the future.

Methods: A systematic review was conducted according to the PRISMA statement.

Results: The limited evidence in the literature was heterogeneous and of low quality. Thus, no formal data meta-analysis could be performed. Procedural stroke was classified as hemorrhagic or ischemic; the latter was subclassified as hemodynamic, embolic (carotid embolic or cardioembolic) or carotid occlusion derived, using a combination of clinical inference and imaging data. Most events occurred in the first 24 hours after the procedure and were related to hypoperfusion (pooled incidence 10.2% [95% confidence interval (CI), 3.0-17.5] vs 13.9% [95% CI, 0.0-60.9] after CEA vs carotid artery stenting events, respectively) or atheroembolism (28.9% [95% CI, 10.9-47.0]) vs 34.3 [95% CI, 0.0-91.5]). After the first 24 hours, hemorrhagic stroke (11.6 [95% CI, 5.7-17.4] vs 9.0 [95% CI, 1.3-16.7]) or thrombotic occlusion (18.4 [95% CI, 0.9-35.8] vs 14.8 [95% CI, 0.0-30.5]) became more likely.

Conclusions: Although procedural stroke incidence and etiology may have changed over the last decades owing to technical improvements and improvements in perioperative monitoring and quality control, the lack of literature data limits further statements. To simplify and enhance future reporting, procedural stroke analysis and classification should be documented preemptively in research settings. We propose a standardized form enclosing reporting standards for procedural stroke with a systematic approach to inference of the most likely etiology, for prospective use in registries and randomized controlled trials on carotid revascularization.
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http://dx.doi.org/10.1016/j.jvs.2021.05.055DOI Listing
June 2021

Long Term Survival and Limb Salvage in Patients With Non-Revascularisable Chronic Limb Threatening Ischaemia.

Eur J Vasc Endovasc Surg 2021 08 2;62(2):225-232. Epub 2021 Jun 2.

Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address:

Objective: The aim of this study was to provide long term survival and limb salvage rates for patients with non-revascularisable (NR) chronic limb threatening ischaemia (CLTI).

Methods: This was a retrospective review of prospectively collected data, derived from a randomised controlled trial (JUVENTAS) investigating the use of a regenerative cell therapy. Survival and limb salvage of the index limb in CLTI patients without viable options for revascularisation at inclusion were analysed retrospectively. The primary outcome was amputation free survival, a composite of survival and limb salvage, at five years after inclusion in the original trial.

Results: In 150 patients with NR-CLTI, amputation free survival was 43% five years after inclusion. This outcome was driven by an equal rate of all cause mortality (35%) and amputation (33%). Amputation occurred predominantly in the first year. Furthermore, 33% of those with amputation subsequently died within the investigated period, with a median interval of 291 days.

Conclusion: Five years after the initial need for revascularisation, about half of the CLTI patients who were deemed non-revascularisable survived with salvage of the index limb. Although the prospects for these high risk patients are still poor, under optimal medical care, amputation free survival seems comparable with that of revascularisable CLTI patients, while the major amputation rate within one year, especially among NR-CLTI patients with ischaemic tissue loss, is very high.
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http://dx.doi.org/10.1016/j.ejvs.2021.04.003DOI Listing
August 2021

Development of a Prediction Model for the Occurrence of Stenosis or Occlusion after Percutaneous Deep Venous Arterialization.

Diagnostics (Basel) 2021 May 31;11(6). Epub 2021 May 31.

Department of Surgery, Northwest Clinics, 1815 JD Alkmaar, The Netherlands.

Percutaneous deep venous arterialization (pDVA) is a promising treatment option in patients with chronic limb-threatening ischemia. Stenosis and occlusions, which are the Achilles' heel of every revascularization procedure, can be treated when detected early. However, frequent monitoring after pDVA is required because when stenosis or occlusions develop is unknown. Therefore, patients currently need to visit the hospital every 2 weeks for surveillance, which can be burdensome. Accordingly, we aimed to develop a model that can predict future stenosis or occlusions in patients after pDVA to be able to create tailor-made follow-up protocols. The data set included 343 peak systolic velocity and 335 volume flow measurements of 23 patients. A stenosis or occlusion developed in 17 patients, and 6 patients remained lesion-free. A statistically significant increase in the risk of stenosis or occlusion was found when duplex ultrasound values decreased 20% within 1 month. The prediction model was also able to estimate a patient-specific risk of future stenosis or occlusions. This is promising for the possibility of reducing the frequency of follow-up visits for low-risk patients and increasing the frequency for high-risk patients. These observations are the starting point for individual surveillance programs in post-pDVA patients. Future studies with a larger cohort are necessary for validation of this model.
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http://dx.doi.org/10.3390/diagnostics11061008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226684PMC
May 2021

Common Variants Associated With Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans.

Front Cardiovasc Med 2021 20;8:658915. Epub 2021 Apr 20.

Central Diagnostics Laboratory, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands.

Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in and its receptors, and , on overall plaque vulnerability, plaque phenotype, intraplaque and expression, coronary artery calcification burden and cardiovascular disease susceptibility. We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreased expression and that rs10491509 (A allele) was associated with increased expression in arterial tissues. No variant was significantly associated with expression. We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β = 0.118 ± s.e. = 0.040, = 3.00 × 10, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β = 0.248 ± s.e. = 0.088, = 4.66 × 10, C allele) and collagen content (β = -0.259 ± s.e. = 0.095, = 6.22 × 10, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaque expression. Neither was intraplaque expression associated with plaque vulnerability and no known eQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in the locus. Our study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.
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http://dx.doi.org/10.3389/fcvm.2021.658915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093786PMC
April 2021

Apparent treatment resistant hypertension and the risk of recurrent cardiovascular events and mortality in patients with established vascular disease.

Int J Cardiol 2021 Jul 29;334:135-141. Epub 2021 Apr 29.

Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Aim: To quantify the relation between apparent treatment resistant hypertension (aTRH) and the risk of recurrent major adverse cardiovascular events (MACE including stroke, myocardial infarction and vascular death) and mortality in patients with stable vascular disease.

Methods: 7455 hypertensive patients with symptomatic vascular disease were included from the ongoing UCC-SMART cohort between 1996 and 2019. aTRH was defined as an office blood pressure ≥140/90 mmHg despite treatment with ≥3 antihypertensive drugs including a diuretic. Cox proportional hazard models were used to quantify the relation between aTRH and the risk of recurrent MACE and all-cause mortality. In addition, survival for patients with aTRH was assessed, taking competing risk of non-vascular mortality into account.

Results: A total of 1557 MACE and 1882 deaths occurred during a median follow-up of 9.0 years (interquartile range 4.8-13.1 years). Compared to patients with non-aTRH, the 614 patients (8%) with aTRH were at increased risk of cardiovascular mortality (HR 1.27; 95% CI 1.03-1.56) and death from any cause (HR 1.25; 95% CI 1.07-1.45) but not recurrent MACE (HR 1.13; 95% CI 0.95-1.34). At the age of 50 years, patients with aTRH after a first cardiovascular event on average had a 6.4 year shorter median life expectancy free of recurrent MACE than patients with non-aTRH.

Conclusion: In hypertensive patients with clinically manifest vascular disease, aTRH is related to a higher risk of vascular death and death from any cause. Moreover, patients with aTRH after a first cardiovascular event have a 6.4 year shorter median life expectancy free of recurrent cardiovascular disease.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.047DOI Listing
July 2021

Joint Associations Between Body Mass Index and Waist Circumference With Atrial Fibrillation in Men and Women.

J Am Heart Assoc 2021 04 15;10(8):e019025. Epub 2021 Apr 15.

Clinical Trial Service Unit and Epidemiological Studies Unit Nuffield Department of Population Health University of Oxford United Kingdom.

Background Associations between adiposity and atrial fibrillation (AF) might differ between sexes. We aimed to determine precise estimates of the risk of AF by body mass index (BMI) and waist circumference (WC) in men and women. Methods and Results Between 2008 and 2013, over 3.2 million adults attended commercial screening clinics. Participants completed health questionnaires and underwent physical examination along with cardiovascular investigations, including an ECG. We excluded those with cardiovascular and cardiac disease. We used multivariable logistic regression and determined joint associations of BMI and WC and the risk of AF in men and women by comparing likelihood ratio χ statistics. Among 2.1 million included participants 12 067 (0.6%) had AF. A positive association between BMI per 5 kg/m increment and AF was observed, with an odds ratio of 1.65 (95% CI, 1.57-1.73) for men and 1.36 (95% CI, 1.30-1.42) for women among those with a BMI above 20 kg/m. We found a positive association between AF and WC per 10 cm increment, with an odds ratio of 1.47 (95% CI, 1.36-1.60) for men and 1.37 (95% CI, 1.26-1.49) for women. Improvement of likelihood ratio χ was equal after adding BMI and WC to models with all participants. In men, WC showed stronger improvement of likelihood ratio χ than BMI (30% versus 23%). In women, BMI showed stronger improvement of likelihood ratio χ than WC (23% versus 12%). Conclusions We found a positive association between BMI (above 20 kg/m2) and AF and between WC and AF in both men and women. BMI seems a more informative measure about risk of AF in women and WC seems more informative in men.
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http://dx.doi.org/10.1161/JAHA.120.019025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174185PMC
April 2021

Common Genetic Variation in MC4R Does Not Affect Atherosclerotic Plaque Phenotypes and Cardiovascular Disease Outcomes.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Department Medicine, Division Endocrinology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

We analyzed the effects of the common BMI-increasing melanocortin 4 receptor (MC4R) rs17782313-C allele with a minor allele frequency of 0.22-0.25 on (1) cardiovascular disease outcomes in two large population-based cohorts (Copenhagen City Heart Study and Copenhagen General Population Study, = 106,018; and UK Biobank, = 357,426) and additionally in an elderly population at risk for cardiovascular disease ( = 5241), and on (2) atherosclerotic plaque phenotypes in samples of patients who underwent endarterectomy ( = 1439). Using regression models, we additionally analyzed whether potential associations were modified by sex or explained by changes in body mass index. We confirmed the BMI-increasing effects of +0.22 kg/m per additional copy of the C allele ( < 0.001). However, we found no evidence for an association of common MC4R genetic variation with coronary artery disease (HR 1.03; 95% CI 0.99, 1.07), ischemic vascular disease (HR 1.00; 95% CI 0.98, 1.03), myocardial infarction (HR 1.01; 95% CI 0.94, 1.08 and 1.02; 0.98, 1.07) or stroke (HR 0.93; 95% CI 0.85, 1.01), nor with any atherosclerotic plaque phenotype. Thus, common MC4R genetic variation, despite increasing BMI, does not affect cardiovascular disease risk in the general population or in populations at risk for cardiovascular disease.
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http://dx.doi.org/10.3390/jcm10050932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957774PMC
March 2021

Blunt popliteal artery injury following tibiofemoral trauma: vessel-first and bone-first strategy.

Eur J Trauma Emerg Surg 2021 Mar 20. Epub 2021 Mar 20.

Department of Orthopedic Surgery, Harvard Medical School Orthopedic Trauma Initiative, Massachusetts General Hospital, 55 Fruit Street, Boston, USA.

Purpose: Blunt popliteal artery injury (BPAI) is a potentially limb-threatening sequela of tibiofemoral (knee) dislocations and fractures. Associated amputation rates for all popliteal artery (PA) injuries range between 10 and 50%. It is unclear whether PA repair or bone stabilization should be performed first. We analyzed (long-term) clinical outcomes of BPAI patients that received initial PA repair (vessel-first, VF) versus initial external stabilization (bone-first, BF).

Methods: Retrospectively, all surgically treated BPAI patients between January 2000 and January 2019, admitted to two level 1 trauma centers were included. Clinical outcomes were determined, stratified by initial management strategy (VF and BF). Treatment strategy was determined by surgeon preference, based on associated injuries and ischemia duration. Primary outcomes (amputation and mortality) and secondary outcomes (claudication and complications) were determined.

Results: Of 27 included BPAI patients, 15 were treated according to the VF strategy (56%) and 12 according to the BF strategy (44%). Occlusion was the most frequently encountered BPAI in 18/27 patients (67%). Total delay and in-hospital delay were comparable between groups (p = 1.00 and p = 0.82). Revascularization was most frequently performed by PA bypass (59%). All patients had primary limb salvage during admission (100%). One secondary amputation due to knee pain was performed in the BF group (4%). During a median clinical follow-up period of 2.7 years, three PA re-interventions were performed, two in the BF group and one in the VF group. None suffered from (intermittent) claudication.

Conclusion: Blunt popliteal artery injury (BPAI) is a rare surgical emergency. Long-term outcomes of early revascularization for BPAI appear to be good, independent of initial management strategy. The BF strategy may be preferred in case of severe orthopedic injury, if allowed by total ischemia duration.
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http://dx.doi.org/10.1007/s00068-021-01632-0DOI Listing
March 2021

End-stage kidney disease in patients with clinically manifest vascular disease; incidence and risk factors: results from the UCC-SMART cohort study.

J Nephrol 2021 10 13;34(5):1511-1520. Epub 2021 Mar 13.

Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Patients with cardiovascular disease (CVD) are at increased risk of end-stage kidney disease (ESKD). Insights into the incidence and role of modifiable risk factors for end-stage kidney disease may provide means for prevention in patients with cardiovascular disease.

Methods: We included 8402 patients with stable cardiovascular disease. Incidence rates (IRs) for end-stage kidney disease were determined stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of end-stage kidney disease for the different determinants.

Results: Sixty-five events were observed with a median follow-up of 8.6 years. The overall incidence rate of end-stage kidney disease was 0.9/1000 person-years. Patients with polyvascular disease had the highest incidence rate (1.8/1000 person-years). Smoking (Hazard ratio (HR) 1.87; 95% CI 1.10-3.19), type 2 diabetes (HR 1.81; 95% CI 1.05-3.14), higher systolic blood pressure (HR 1.37; 95% CI 1.24-1.52/10 mmHg), lower estimated glomerular filtration rate (eGFR) (HR 2.86; 95% CI 2.44-3.23/10 mL/min/1.73 m) and higher urine albumin/creatinine ratio (uACR) (HR 1.19; 95% CI 1.15-1.23/10 mg/mmol) were independently associated with elevated risk of end-stage kidney disease. Body mass index (BMI), waist circumference, non-HDL-cholesterol and exercise were not independently associated with risk of end-stage kidney disease.

Conclusions: Incidence of end-stage kidney disease in patients with cardiovascular disease varies according to vascular disease location. Several modifiable risk factors for end-stage kidney disease were identified in patients with cardiovascular disease. These findings highlight the potential of risk factor management in patients with manifest cardiovascular disease.
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http://dx.doi.org/10.1007/s40620-021-00996-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494654PMC
October 2021

Strengths and obvious limitations of transcervical carotid artery revascularization.

J Vasc Surg 2021 03;73(3):1110

Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

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http://dx.doi.org/10.1016/j.jvs.2020.08.153DOI Listing
March 2021

Utility of risk prediction models to detect atrial fibrillation in screened participants.

Eur J Prev Cardiol 2021 May;28(6):586-595

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford OX3 7LF, UK.

Aims: Atrial fibrillation (AF) is associated with higher risk of stroke. While the prevalence of AF is low in the general population, risk prediction models might identify individuals for selective screening of AF. We aimed to systematically identify and compare the utility of established models to predict prevalent AF.

Methods And Results: Systematic search of PubMed and EMBASE for risk prediction models for AF. We adapted established risk prediction models and assessed their predictive performance using data from 2.5M individuals who attended vascular screening clinics in the USA and the UK and in the subset of 1.2M individuals with CHA2DS2-VASc ≥2. We assessed discrimination using area under the receiver operating characteristic (AUROC) curves and agreement between observed and predicted cases using calibration plots. After screening 6959 studies, 14 risk prediction models were identified. In our cohort, 10 464 (0.41%) participants had AF. For discrimination, six prediction model had AUROC curves of 0.70 or above in all individuals and those with CHA2DS2-VASc ≥2. In these models, calibration plots showed very good concordance between predicted and observed risks of AF. The two models with the highest observed prevalence in the highest decile of predicted risk, CHARGE-AF and MHS, showed an observed prevalence of AF of 1.6% with a number needed to screen of 63. Selective screening of the 10% highest risk identified 39% of cases with AF.

Conclusion: Prediction models can reliably identify individuals at high risk of AF. The best performing models showed an almost fourfold higher prevalence of AF by selective screening of individuals in the highest decile of risk compared with systematic screening of all cases.

Registration: This systematic review was registered (PROSPERO CRD42019123847).
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http://dx.doi.org/10.1093/eurjpc/zwaa082DOI Listing
May 2021

The Voyager PAD Trial in a Surgical Perspective: A Debate.

Eur J Vasc Endovasc Surg 2021 05 13;61(5):721-722. Epub 2021 Feb 13.

Department of Surgery, Sint Antonius Ziekenhuis Nieuwegein, Nieuwegein, The Netherlands.

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http://dx.doi.org/10.1016/j.ejvs.2021.01.020DOI Listing
May 2021

Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease.

Int J Cardiovasc Imaging 2021 Jun 12;37(6):2051-2061. Epub 2021 Feb 12.

Department of Radiology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, The Netherlands.

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28-4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59-0.72). Calibration for models II-V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59-29.39)) and model V (NRI 20.00% (95%CI 5.59-34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.
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http://dx.doi.org/10.1007/s10554-021-02164-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255266PMC
June 2021
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