Eversion technique versus conventional endarterectomy with patch angioplasty in carotid surgery: protocol for a systematic review with meta-analyses and trial sequential analysis of randomised clinical trials

Introduction Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of patch angioplasty to restore the arterial wall after longitudinal endarterectomy is, to date, not unequivocally proven to be superior to eversion technique. A systematic review is needed for evaluation of benefits and harms of the eversion technique versus the traditional endarterectomy with patch angioplasty in patients with symptomatic carotid stenosis. Methods and outcomes The review will be conducted according to this protocol following the recommendations of the 'Cochrane Handbook for Systematic Reviews' and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Randomised clinical trials comparing eversion technique versus endarterectomy with patch angioplasty in patients with a symptomatic stenosis of the internal carotid artery will be included. Primary outcomes are all-cause mortality rate, health-related quality of life and serious adverse events. Secondary outcomes are 30-day stroke and mortality rate, symptomatic arterial restenosis or occlusion and non-serious adverse events. The databases Cochrane Central Register of Controlled Trials, PubMed/MEDLINE and EMBASE will be searched (November 2019). We will primarily base our conclusions on meta-analyses of trials with overall low-risk of bias. We will use trial sequential analysis to assist the evaluation of imprecision in Grading of Recommendations, Assessment, Development and Evaluation. However, if pooled point estimates of all trials are similar to pooled point estimates of trials with overall low risk of bias and there is lack of a statistical significant interaction between estimates from trials with overall high risk of bias and trials with overall low risk of bias we will consider the trial sequential analysis adjusted precision of the estimate achieved in all trials as the result of our meta-analyses. Ethics and dissemination The proposed systematic review will collect and analyse data from published studies, therefore, ethical approval is not required. The results of the review will be disseminated by publication in a peer-review journal and submitted for presentation at conferences. PROSPERO registration number CRD42019119361

A Comparison of Quality of Life in Elderly Patients with Intermittent Claudication and Chronic Limb-Threatening Ischemia

BACKGROUND: Intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI) are both associated with a decreased health status and possibly quality of life (QOL). A better understanding of the differences in QOL between patients with IC and CLTI could be of additional value in shared decision-making. The aim of this study was to compare the QOL at baseline between patients with IC and patients with CLTI. METHODS: The study population was based on 2 study cohorts, 1 cohort consisted of patients with IC (ELECT registry) and the other cohort of patients with CLTI (KOP-study). Patients with an age of ≥70 years were included. QOL at baseline was measured by the WHOQOL-BREF questionnaire. Nonresponders were excluded from data analyses. Student's t-tests and analysis of covariance (ANCOVA) analyses were used to compare QOL between the 2 groups. Outcomes of the ANCOVA analyses were expressed as estimated marginal means. RESULTS: In total, 308 patients were included, 115 patients with IC and 193 patients with CLTI. Patients with CLTI were older (median age 80 years vs. 75 years, P < 0.001) and had more comorbidities. Patients with IC had a statistically significant higher QOL regarding physical health (mean 13.7 [standard deviation (SD) 2.3] vs. 10.8 [SD 2.8], P < 0.001), psychological health (mean 15.3 [SD 2.1] vs. 14.1 [SD 2.4], P < 0.001), environment (mean 16.3 [SD 2.4] vs. 15.5 [SD 2.0], P < 0.002), and the overall domain (mean 3.5 [SD 0.7] vs. 3.1 [SD 0.9], P < 0.001). After correcting for the confounding effect of age and sex, patients with IC still had a statistically significant higher QOL in the physical, psychological, environment, and overall domain. CONCLUSIONS: Patients with IC had a significantly higher QOL in the physical, psychological, environment, and overall domains of the WHOQOL-BREF questionnaire compared with patients with CLTI. This underlines the importance of strategies that reduce disease progression as disease progression is associated with a decrease in QOL

Protocol for a prospective, longitudinal cohort study on the effect of arterial disease level on the outcomes of supervised exercise in intermittent claudication: the ELECT Registry

Introduction  Despite guideline recommendations advocating conservative management before invasive treatment in intermittent claudication, early revascularisation remains widespread in patients with favourable anatomy. The aim of the Effect of Disease Level on Outcomes of Supervised Exercise in Intermittent Claudication Registry is to determine the effect of the location of stenosis on the outcomes of supervised exercise in patients with intermittent claudication due to peripheral arterial disease. Methods and analysis  This multicentre prospective cohort study aims to enrol 320 patients in 10 vascular centres across the Netherlands. All patients diagnosed with intermittent claudication (peripheral arterial disease: Fontaine II/Rutherford 1-3), who are considered candidates for supervised exercise therapy by their own physicians are appropriate to participate. Participants will receive standard care, meaning supervised exercise therapy first, with endovascular or open revascularisation in case of insufficient effect (at the discretion of patient and vascular surgeon). For the primary objectives, patients are grouped according to anatomical characteristics of disease (aortoiliac, femoropopliteal or multilevel disease) as apparent on the preferred imaging modality in the participating centre (either duplex, CT angiography or magnetic resonance angiography). Changes in walking performance (treadmill tests, 6 min walk test) and quality of life (QoL; Vascular QoL Questionnaire-6, WHO QoL Questionnaire-Bref) will be compared between groups, after multivariate adjustment for possible confounders. Freedom from revascularisation and major adverse cardiovascular disease events, and attainment of the treatment goal between anatomical groups will be compared using Kaplan-Meier survival curves. Ethics and dissemination  This study has been exempted from formal medical ethical approval by the Medical Research Ethics Committees United 'MEC-U' (W17.071). Results are intended for publication in peer-reviewed journals and for presentation to stakeholders nationally and internationally

A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation

Contains fulltext : 118070.pdf (publisher's version ) (Open Access)Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day) simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFkappaB regulated mediators (i.e. IL-6 (P<0.001) and MCP-1 (P<0.001)); shifted macrophage polarization towards a M2 phenotype (P<0.0003); selectively reduced macrophage-related markers such as cathepsin K and S (P<0.009 and 0.0027 respectively), and ALOX5 (P<0.0009), and reduced vascular wall NFkappaB activity (40 mg/day group, P<0.016). No effect was found on other cell types. Evaluation of the clinical efficacy of statins to reduce AAA progression did not indicate an effect of statins on aneurysm growth (P<0.337). Hence, in the context of AAA the clinical relevance of statins pleiotropy appears minimal

The effect of statin treatment on aortic wall MCP-1, Il-6 and IL-8 levels.

<p>Non-treated controls (white bars); 20 mg statin treated (grey bars) and 40 mg statin treated (black bars). ^*) significant and dose dependent reduction, P<0.0003. NS: not significant.</p

Relative mRNA expression (log transcript level relative to GAPDH (GAPDH = 0)) of inflammatory mediators, cell activation markers and proteases and the MMP inhibitor TIMP-1.

<p>Mean (sd) or median [IQR].</p>*<p>P value is for a linear trend between the groups in case of normally distributed data (general linear model in one-way ANOVA), or for the Kruskal Wallis test in case of non-normal distributed data.</p>*)<p>significance reached after the Benjamini and Hochberg False Discovery Rate correction.</p

The effect of statin therapy on aneurysm progression (mean, 95% confidentiality interval in mm/year).

<p>A: corrected for base line diameter, age and gender (P<0.36); B is correction A plus correction for diabetes mellitus, history cardiovascular disease, anti hypertensives, aspirin and smoking (P<0.34); and C is correction B plus correction for cholesterol (P<0.89).</p

Relative aortic wall cathepsin K and S expression assessed by Western blot analysis (normalized on basis of actin levels).

<p>*Levels significantly reduced compared to non-treated controls, P<0.034.</p

There is a strong correlation between aortic wall IL-6 and MCP-1 levels, p<0.0001.

<p>Black circles: controls; Open circles: Simvastatin/Atorvastatin 20 mg, Grey circles: Simvastatin/Atorvastatin 20 mg.</p