Background and aims: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids,... Show moreBackground and aims: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples. Methods: We used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology. Results: Lipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas. Conclusions: By comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies. Show less
Clinical audits are used to measure and improve quality of care. Since 2013 all patients undergoing aortic abdominal aneurysm (AAA) surgery in the Netherlands are registered Dutch Surgical Aneurysm... Show moreClinical audits are used to measure and improve quality of care. Since 2013 all patients undergoing aortic abdominal aneurysm (AAA) surgery in the Netherlands are registered Dutch Surgical Aneurysm Audit (DSAA). Where postoperative mortality was originally the primary outcome measure of this audit, due to low event rates this turned out to be indistinguishable between hospitals and did not provide any leads for quality improvement. With the aim of improving the quality of AAA surgery, new quality measures regarding the indication for surgery, choice of treatment and surgical outcomes were investigated in this thesis.Following the example of the DSAA, the Dutch Audit for Carotid Interventions (DACI) was initiated to monitor quality of care in patients undergoing carotid interventions. In this thesis the results of patients with a symptomatic carotid artery stenosis undergoing surgery during the first years of auditing are described. Show less
Objective: Composite measures may better objectify hospital performance than individual outcome measures (IOM). Textbook outcome (TO) is an outcome measure achieved for an individual patient when... Show moreObjective: Composite measures may better objectify hospital performance than individual outcome measures (IOM). Textbook outcome (TO) is an outcome measure achieved for an individual patient when all undesirable outcomes are absent. The aim of this study was to assess TO as an additional outcome measure to evaluate quality of care in symptomatic patients treated by carotid endarterectomy (CEA).Methods: All symptomatic patients treated by CEA in 2018, registered in the Dutch Audit for Carotid Interventions, were included. TO was defined as a composite of the absence of 30 day mortality, neurological events (any stroke or transient ischaemic attack [TIA]), cranial nerve deficit, haemorrhage, 30 day readmission, prolonged length of stay (LOS; > 5 days) and any other surgical complication. Multivariable logistic regression was used to identify covariables associated with achieving TO, which were used for casemix adjustment for hospital comparison. For each hospital, an observed vs. expected number of events ratio (O/E ratio) was calculated and plotted in a funnel plot with 95% control limits.Results: In total, 70.7% of patients had a desired outcome within 30 days after CEA and therefore achieved TO. Prolonged LOS was the most common parameter (85%) and mortality the least common (1.1%) for not achieving TO. Covariates associated with achieving TO were younger age, the absence of pulmonary comorbidity, higher haemoglobin levels, and TIA as index event. In the case mix adjusted funnel plot, the O/E ratios between hospitals ranged between 0.63 and 1.27, with two hospitals revealing a statistically significantly lower rate of TO (with O/E ratios of 0.63 and 0.66).Conclusion: In the Netherlands, most patients treated by CEA achieve TO. Variation between hospitals in achieving TO might imply differences in performance. TO may be used as an additive to the pre-existing IOM, especially in surgical care with low baseline risk such as CEA. Show less
Objective: The objective of this study was to determine the clinical relevance of postcarotid endarterectomy hypertension (PEH) by investigating the effect of PEH on hospital length of stay (LOS)... Show moreObjective: The objective of this study was to determine the clinical relevance of postcarotid endarterectomy hypertension (PEH) by investigating the effect of PEH on hospital length of stay (LOS) and by investigating short-term and long-term complications of PEH. In addition, risk factors for PEH were determined.Methods: A single-center retrospective cohort study was performed. Demographic, preoperative, intraoperative, and postoperative outcomes of 192 patients undergoing carotid endarterectomy were evaluated. Outcomes were compared between patients with PEH and patients without PEH. PEH was defined as an acute systolic blood pressure (SBP) rise >170 mm Hg or persistent SBP >150 mm Hg on the ward and leading to the consultation of an internist. The overall survival and event-free survival were compared using a Kaplan-Meier analysis and a Cox regression analysis. A multivariate logistic regression analysis was performed to determine risk factors for PEH.Results: PEH developed in 44 of 192 patients (25%). Preoperative hypertension (SBP >150 mm Hg) was determined to be a risk factor for PEH (odds ratio, 3.3; 95% confidence interval [CI], 1.6-6.9). Hospital LOS was prolonged in patients with PEH compared with patients without PEH (median LOS of 5 days vs 3 days, respectively; P <.001). No difference in the occurrence of ischemic neurologic events or rebleeding during hospitalization was observed (P =.58 and P =.72, respectively). Cardiovascular and ischemic neurologic events during follow-up did not occur more often in patients with PEH than in patients without PEH (P =.46). There was no difference in mortality between the PEH and non-PEH groups (hazard ratio, 1.6; 95% CI, 0.6-4.3). The same applies to the event-free survival (hazard ratio, 0.77; 95% CI, 0.4-1.7). Combined event-free survival for stroke and myocardial infarction was 92% (95% CI, 87%-97%) at 2 years for patients without PEH and 86% (95% CI, 74%-98%) at 2 years for patients with PEH (P =.25). Event-free survival for mortality was 90% (95% CI, 85%-96%) at 2 years for patients without PEH and 94% (95% CI, 86%-100%) at 2 years for patients with PEH (P =.36).Conclusions: Patients with PEH had a significant increase in hospital LOS. However, adverse short-term and long-term events did not occur more often in patients with PEH. High preoperative SBP was identified as a risk factor for PEH; no other demographic and clinical variables were associated with PEH. Show less
Objectives: As the risk of a recurrent neurological event in patients with symptomatic carotid stenosis requiring carotid endarterectomy (CEA) is highest in the early phase after the first... Show moreObjectives: As the risk of a recurrent neurological event in patients with symptomatic carotid stenosis requiring carotid endarterectomy (CEA) is highest in the early phase after the first neurological event, guidelines recommend operating on these patients as soon as possible or at least within 14 days of their initial event. However, in real world practice this is often not met. The aim of this study is to identify factors that cause hospital dependent delay to CEA.Methods: All consecutive patients with symptomatic carotid stenosis undergoing CEA registered in the mandatory Dutch Audit for Carotid Interventions from January 2014 up to and including December 2017 were included in the current analysis. Univariable followed by multivariable logistic regression was used to identify independent factors associated with hospital dependent waiting time, defined as time from the first consultation at any hospital to CEA of more than 14 days.Results: A total of 8620 patients were included. The median time to CEA was 11 days (IQR 8-14). Seventy-eight per cent of patients underwent CEA within 14 days of first hospital consultation. Factors associated with a hospital dependent waiting time longer than 14 days were age (OR 0.99 per year, 95% CI 0.98-0.99), any previous CEA (OR 1.67, 95% CI 1.32-2.09), ocular symptoms as index event (OR 1.31, 95% CI 1.15-1.50), and indirect referral (OR 1.53, 95% CI 1.34-1.73). Hospital surgical volume was not identified as a factor for delay, except for the delay of indirectly referred patients where high volume hospitals reported the shortest delay.Conclusion: This cohort derived from a validated nationwide prospective audit identified younger age, previous CEA, ocular symptoms, and indirect referral as hospital dependent factors for delay. High volume hospitals had a similar hospital dependent waiting time to middle and low volume hospitals. However, high volume hospitals had more indirect referrals, implying that their logistics are more efficiently organised. Show less
