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A collection of Open Access and Embargoed publications from Utrecht University Repository. For an explanation on how and where to find an Open Access version of a publication see the information on this page.

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    Long-term risk of major adverse cardiovascular events after carotid endarterectomy-a 9-year prospective cohort study of the Athero-Express biobank
    (SAGE Publications Inc., 2026-06) Mol, Barend M; de Bresser, Carolijn J M; de Kleijn, P V; Vaartjes, Ilonca; Pasterkamp, Gerard; Bots, Michiel L; de Borst, Gert J; Poorthuis, Michiel H F; Koop, Yvonne; Zorgeenheid Vaatchirurgie Medisch; Poli Van Creveldkliniek Medisch; Cardiovasculaire Epidemiologie; Circulatory Health; JC onderzoeksprogramma Cardiovascular Health; Centraal Diagnostisch Laboratorium; Programmabureau Zorg van Morgen; Cardiovasculaire Epi Team 5; Epidemiology & Health Economics; Regenerative Medicine and Stem Cells; Opleiding Neurologie; Cancer
    INTRODUCTION: Carotid endarterectomy (CEA) is performed to lower the long-term risk of stroke in patients with carotid stenosis. Data evaluating long-term outcomes after CEA are scarce, but crucial for accurately determining long-term benefits. We aimed to estimate the long-term risk of major adverse cardiovascular and cerebrovascular events (MACE) after CEA. PATIENTS AND METHODS: A data linkage study was performed using patients from the Athero-Express biobank study who underwent CEA in two Dutch tertiary referral hospitals between 2002 and 2020. Data were linked to the Cause of Death Register, Population Register from Statistics Netherlands and the Hospital Discharge Register. The primary outcome was the occurrence of MACE at any time during follow-up and in the postprocedural (beyond 30 days) period. RESULTS: CEA was performed in 2123 unique patients; linkage was possible for 1876. Median age was 70 years, 70% was male, and 87% had a symptomatic stenosis. MACE occurred in 455 patients (24.3%) during 9.2 years median follow-up. Five and 10-year cumulative incidence of MACE was 14.3% and 26.4%, respectively. Vascular death was the predominant contributor to MACE with 246 events (54.1%). Older age, current smoking, lower estimated glomerular filtration rate, diabetes mellitus and coronary artery disease (CAD) were associated with an increased risk of MACE. Preoperative antiplatelet use was associated with decreased risk of MACE. Patients with ischaemic stroke as qualifying event were at higher risk of MACE (P = .018). The incidence rate of MACE did not change over time (P = .9). DISCUSSION: Patients remain at high risk of MACE after CEA, especially of vascular death and in older patients, current smokers and patients with diabetes or CAD. CONCLUSION: These findings underscore the need to enhance cardiovascular preventive strategies following CEA, in order to optimise long-term benefit.
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    Reduced relapse rate in upfront tandem autologous/reduced-intensity allogeneic transplantation in multiple myeloma only results in borderline non-significant prolongation of progression-free but not overall survival
    (Ferrata Storti Foundation, 2015) Lokhorst, Henk M.; Van Der Holt, Bronno; Cornelissen, Jan J.; Kersten, Marie José; Van Oers, Marinus; Raijmakers, Reinier; Minnema, Monique C.; Zweegman, Sonja; Bos, Gerard; Schaap, Nicolaas; Wittebol, Shulamiet; de Weerdt, Okke; Ammerlaan, Rianne; Sonneveld, Pieter; MS Hematologie; Other research (not in main researchprogram); Infection & Immunity
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    Reply to: Breast cancer risk in MEN1--a cancer genetics perspective
    (Wiley-Blackwell Publishing Ltd, 2015-07) Dreijerink, Koen M A; Valk, Gerlof D.; MS Endocriene Oncologie; Cancer; Other research (not in main researchprogram)
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    Rich club organization and cognitive performance in healthy older participants
    (MIT Press, 2015) Baggio, Hugo C.; Segura, Barbara; Junque, Carme; De Reus, Marcel A.; Sala-Llonch, Roser; Van Den Heuvel, Martijn P.; Onderzoeksgroep 6; Brain
    The human brain is a complex network that has been noted to contain a group of densely interconnected hub regions. With a putative “rich club” of hubs hypothesized to play a central role in global integrative brain functioning, we assessed whether hub and rich club organizations are associated with cognitive performance in healthy participants and whether the rich club might be differentially involved in cognitive functions with a heavier dependence on global integration. A group of 30 relatively older participants (range = 39-79 years of age) underwent extensive neuropsychological testing, combined with diffusion-weighted magnetic resonance imaging to reconstruct individual structural brain networks. Rich club connectivity was found to be associated with general cognitive performance. More specifically, assessing the relationship between the rich club and performance in two specific cognitive domains, we found rich club connectivity to be differentially associated with attention/executive functions—known to rely on the integration of distributed brain areas—rather than with visuospatial/visuoperceptual functions, which have a more constrained neuroanatomical substrate. Our findings thus provide first empirical evidence of a relevant role played by the rich club in cognitive processes.
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    Population Pharmacokinetic Analysis of Enalapril and Enalaprilat in Newly Treated Children with Heart Failure: Implications for Safe Dosing of Enalapril (LENA Studies)
    (Adis, 2025-07) Steichert, Melina; Cawello, Willi; Laeer, Stephanie; the LENA Consortium; Pathologie; Cardiologie onderzoek 1; Child Health; Circulatory Health
    Background: Enalapril orodispersible minitablets (ODMT) have been authorised by the European Medicines Agency for the treatment of heart failure in children from birth to 17 years of age in 2023. Consequently, the use of enalapril in very young and angiotensin-converting enzyme inhibitor (ACEi) naïve patients is expected to increase. Objectives: Simultaneous characterisation of the pharmacokinetics (PK) of enalapril and the active metabolite enalaprilat in ACEi naïve children with heart failure using a combined population pharmacokinetic (PopPK) model and identification of clinically relevant covariates for the dosing of enalapril in this population. Methods: Data of ACEi naïve subjects from the European project ‘Labeling of Enalapril from Neonates up to Adolescents’ (LENA) were analysed using nonlinear mixed effects modelling. In the prospective, open-label, multicentre phase II/III PK bridging studies, children with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) received enalapril ODMT according to an age- and weight-dependent dosing regimen. Allometric scaling was implemented for the disposition parameters of enalapril and enalaprilat. Stepwise covariate modelling was used to test the covariates age, sex, serum creatinine and Ross score. The final model was validated using nonparametric bootstrap analysis. Simulations were performed to assess the impact of the covariates after the first dose and at steady state. Results: The analysed dataset comprised 173 enalapril and 268 enalaprilat serum concentrations from 34 subjects aged 25 days to 2.1 years (median age = 0.3 years). A combined model consisting of a one-compartment model for enalapril coupled with a one-compartment model for enalaprilat with absorption lag was selected as the structural model. Covariate analysis revealed that the weight-adjusted apparent clearance of enalaprilat increases with increasing age and decreases with increasing serum creatinine. In addition, the weight-adjusted apparent volume of distribution of enalaprilat decreases with increasing Ross score. The simulations indicated that serum creatinine levels above the normal reference range, age and weight were clinically relevant covariates for both the first dose and the steady state dose of enalapril. Furthermore, the simulations indicated that the Ross score is a clinically relevant covariate for the first dose of enalapril. Conclusions: The results of the PopPK analysis and simulations indicated that, in addition to the currently considered parameters of weight and renal function, the parameters of age and severity of heart failure should also be considered when dosing enalapril in children with heart failure. Trial Registration: Trial registration number (date of registration): EudraCT 2015-002335-17 (30 November 2015), EudraCT 2015-002396-18 (30 November 2015). The trials were registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu).