De uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische... Show moreDe uitkomsten beschreven in dit proefschrift dragen bij aan de bestaande overtuiging dat een verfijndere classificatie voor depressie, op basis van symptoomprofielen en hun mogelijke biologische onderbouwing, overwogen dient te worden. Inmiddels wordt adipositas in de dagelijkse praktijk op meer dan alleen het BMI beoordeeld, namelijk ook de tailleomtrek en het lipidenprofiel. Echter, dergelijke aandacht bestaat nog niet voor de heterogeniteit van depressie. Een grotere bewustwording van de verschillende manifestaties van depressie-symptomatologie, die het gevolg kunnen zijn van uiteenlopende pathofysiologische mechanismen, is van essentieel belang. Wanneer een patiënt met depressie een atypisch energie-gerelateerd symptoomprofiel heeft, kan het nuttig zijn om diens metabole biomarkers te controleren om mogelijke ontwikkeling van cardiometabole ziekten te voorkomen. In de klinische praktijk moeten wij ons bij de behandeling van patiënten met depressie ook meer bewust worden van de correlatie tussen symptoomprofielen van depressie en afzonderlijke biologische en klinische manifestaties. Het is cruciaal om goed te kijken naar de symptomen die bij elke patiënt tot uiting komen. De resultaten van dit proefschrift tonen aan dat patiënten met een depressie die atypische energie-gerelateerde depressieve symptomen vertonen, genetisch en klinisch kwetsbaar zijn voor aan insulineresistentie gerelateerde ziekten (namelijk adipositas, metabole ontregelingen en diabetes mellitus type 2). Een gepersonaliseerde aanpak kan behulpzaam zijn in preventie van deze chronische en complexe ziekten. Hierbij dient er rekening gehouden worden met de heterogeniteit van depressie en de associatie tussen atypische energie-gerelateerde symptomen van depressie en deze ziekten. Show less
In this thesis, novel and established imaging techniques have provided new insights into the pathophysiology and outcomes of various cardiac diseases.In part I, a novel method of evaluating RV... Show moreIn this thesis, novel and established imaging techniques have provided new insights into the pathophysiology and outcomes of various cardiac diseases.In part I, a novel method of evaluating RV function is described and validated. Chapter 2 provides a proof of concept for the feasibility of RV myocardial work assessment on 2-dimensional speckle tracking strain echocardiography. This concept was validated in chapter 3 in a population with precapillary pulmonary hypertension.Part II includes six chapters focused on novel insights into the risk stratification of patients with valvular heart disease. Chapter 4 demonstrates the differences and prognostic implications of LV remodeling in different types of bicuspid aortic valve disease, while chapter 5 shows the association between left atrial enlargement and outcome in patients with aortic regurgitation due to a bicuspid aortic valve. Chapter 6 evaluates the prevalence and prognostic relevance of mitral regurgitation in patients with a bicuspid aortic valve and chapter 7 investigates the importance of LV ejection fraction in patients with bicuspid aortic valve disease. Chapter 8 evaluates the mechanisms linking renal function and significant tricuspid regurgitation. Chapter 9 evaluates the prognostic role of the number of secondary outcome determinants on postsurgical survival in patients with degenerative mitral regurgitation. Show less
BackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic... Show moreBackgroundAffective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands’ immunometabolic health on siblings’ psychological symptoms and on the association between immunometabolic health and these symptoms in siblings.MethodsThe sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering.ResultsIn siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings.ConclusionsOur findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health. Show less
Background: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of... Show moreBackground: Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AFablations, pacemaker implantations and coronary angiography and/or stenting procedures. Method: GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for <2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding <8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy. Results: During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AFcardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%1.36%). Conclusions: More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings. Show less
Dijk, W.B. van; Fiolet, A.T.L.; Schuit, E.; Sammani, A.; Groenhof, T.K.J.; Graaf, R. van der; ... ; Mosterd, A. 2021
Objective: This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of... Show moreObjective: This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial.Study Design and Setting: In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel.Results: Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%).Conclusion: Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information. (C) 2020 The Authors. Published by Elsevier Inc. Show less
BACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was... Show moreBACKGROUND: Depression has been associated with metabolic alterations, which adversely impact cardiometabolic health. Here, a comprehensive set of metabolic markers, predominantly lipids, was compared between depressed and nondepressed persons.METHODS: Nine Dutch cohorts were included, comprising 10,145 control subjects and 5283 persons with depression, established with diagnostic interviews or questionnaires. A proton nuclear magnetic resonance metabolomics platform provided 230 metabolite measures: 51 lipids, fatty acids, and low-molecular-weight metabolites; 98 lipid composition and particle concentration measures of lipoprotein subclasses; and 81 lipid and fatty acids ratios. For each metabolite measure, logistic regression analyses adjusted for gender, age, smoking, fasting status, and lipid-modifying medication were performed within cohort, followed by random-effects meta-analyses.RESULTS: Of the 51 lipids, fatty acids, and low-molecular-weight metabolites, 21 were significantly related to depression (false discovery rate q < .05). Higher levels of apolipoprotein B, very-low-density lipoprotein cholesterol, triglycerides, diglycerides, total and monounsaturated fatty acids, fatty acid chain length, glycoprotein acetyls, tyrosine, and isoleucine and lower levels of high-density lipoprotein cholesterol, acetate, and apolipoprotein Al were associated with increased odds of depression. Analyses of lipid composition indicators confirmed a shift toward less high-density lipoprotein and more very-low-density lipoprotein and triglyceride particles in depression. Associations appeared generally consistent across gender, age, and body mass index strata and across cohorts with depressive diagnoses versus symptoms.CONCLUSIONS: This large-scale meta-analysis indicates a clear distinctive profile of circulating lipid metabolites associated with depression, potentially opening new prevention or treatment avenues for depression and its associated cardiometabolic comorbidity. Show less
Hermans, M.; Roeters van Lennep, J.E.; Daele, P. van; Bot, I. 2019
Mast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which... Show moreMast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which is a hematological disease that is characterized by the accumulation of mast cells due to clonal proliferation. This association suggests an important role for mast cells in cardiovascular disease. Indeed, the evidence establishing the contribution of mast cells to the development and progression of atherosclerosis is continually increasing. Mast cells may contribute to plaque formation by stimulating the formation of foam cells and causing a pro-inflammatory micro-environment. In addition, these cells are able to promote plaque instability by neo-vessel formation and also by inducing intraplaque hemorrhage. Furthermore, mast cells appear to stimulate the formation of fibrosis after a cardiac infarction. In this review, the available data on the role of mast cells in cardiovascular disease are summarized, containing both in vitro research and animal studies, followed by a discussion of human data on the association between cardiovascular morbidity and diseases in which mast cells are important: Kounis syndrome, mastocytosis and allergy. Show less
Thoracale epidurale anesthesie (TEA), ook wel ruggenprik genoemd, zorgt voor een uitstekende pijnstilling rondom operaties en wordt als zodanig veelvuldig toegepast binnen de cardiothoracale... Show moreThoracale epidurale anesthesie (TEA), ook wel ruggenprik genoemd, zorgt voor een uitstekende pijnstilling rondom operaties en wordt als zodanig veelvuldig toegepast binnen de cardiothoracale chirurgie. TEA heeft echter ook effecten op het hart en de bloedsomloop. Hoewel in fysiologische studies is aangetoond dat thoracale epidurale anesthesie gunstige effecten heeft op het hart, heeft zich dit in grote klinische studies niet vertaald in een betere uitkomst. Dit proefschrift beschrijft de anatomie en fysiologie van het hart tijdens TEA bij patiënten die een long ingreep ondergaan. Het doel van dit proefschrift is het bepalen van de bijwerkingen van TEA op het hart en de bloedsomloop waarbij deze effecten van TEA zowel tijdens rust als gedurende omstandigheden van stress (zoals tijdens operatie of inspanning) onderzocht werden. De resultaten van dit proefschrift tonen aan dat TEA de functie van de rechter hartkamer vermindert. Dit proefschrift toont ook aan dat de toename van de linker- en rechter kamerfunctie tijdens inspanning nauwelijks wordt beïnvloed door TEA. Leeftijd lijkt geen duidelijke invloed te hebben op de bijwerkingen van TEA. Het is nog niet duidelijk in hoeverre deze resultaten klinisch relevant zijn. Echter, de resultaten uit dit proefschrift zouden kunnen helpen bij het maken van weloverwogen besluiten rond het gebruik van TEA bij cardiothoracale chirurgie. Show less
Research on the psychological and physiological stress-responses have been unable to fully clarify the underlying relationship. The unconscious stress hypothesis proposes that stress-related... Show moreResearch on the psychological and physiological stress-responses have been unable to fully clarify the underlying relationship. The unconscious stress hypothesis proposes that stress-related processes outside of awareness may negatively affect cardiovascular (CV) health by activating and even prolonging physiological stress-responses. This thesis provides a starting point in the exploration of the role of processes outside of awareness in cardiovascular stress research. The eight chapters discuss the findings of a systematic review and a series of experiments, using subliminal priming paradigms and fear conditioning, and address various theoretical and methodological issues to benefit future studies in this area. It seems evident that what is outside of awareness may influence the physiological state, but not necessarily all health-relevant parameters. The physiological changes related to unconscious stress appears to differ between the various stressful stimuli and stressors used. Show less
Shmuely, S.; Lende, M. van der; Lamberts, R.J.; Sander, J.W.; Thijs, R.D. 2017
This thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients... Show moreThis thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients with chronic kidney disease (CKD) and less ESA-treated patients had a hemoglobin above 12 g/dL. Furthermore it is shown that ESA- treated pre-dialysis patients in the Netherlands received more antihypertensive agents than patients without ESA, confirming the hypertensive effect of ESA. However, no relevant difference in routinely measured blood pressure was observed between patients with and without ESA treatment, thus the hypertensive effect of ESAs could be controlled in clinical practice. In addition, no excess of thrombotic events was shown in ESA-treated dialysis patients compared to patients without ESA treatment. In contrast, a higher risk of cardiovascular events with ESA use was indicated in Danish patients with multiple myeloma and myelodyslastic syndrome. Also, with two analytical approaches, a harmful effect of high ESA doses on mortality was indicated in Dutch dialysis patients. Last, it was shown that ESA resistance was associated with mortality in both hemodialysis and peritoneal dialysis patients. To conclude, treatment with high ESA doses was associated with a higher risk of mortality, but the mechanism is largely unknown. Show less
Loeffen, R.; Winckers, K.; Ford, I.; Jukema, J.W.; Robertson, M.; Stott, D.J.; ... ; PROSPER Study Grp 2015
Cardiovascular safety issues related to changes in blood pressure, arise frequently in drug development. In the thesis __Towards predictive cardiovascular safety __ a systems pharmacology approach_... Show moreCardiovascular safety issues related to changes in blood pressure, arise frequently in drug development. In the thesis __Towards predictive cardiovascular safety __ a systems pharmacology approach__, a system-specific model is described to quantify drug effects on the interrelationship between mean arterial pressure, cardiac output, heart rate, stroke volume and total peripheral resistance in rats. The developed model can be used to quantify and predict the dynamic changes in the cardiovascular system (CVS) and elucidate the mechanism of action of novel compounds. An ultimate application of this system-specific CVS model would be to facilitate the anticipation of the clinical response based on preclinical data for newly developed compounds. Furthermore, the developed system-specific CVS model was combined with receptor models to quantify and predict the cardiovascular effects of the sphingosine 1-phosphate (S1P) receptor agonists, fingolimod-phosphate (fingolimod-P)and siponimod, in rats. This systems pharmacology model provided a quantitative understanding of the cardiovascular effects of fingolimod-P and siponimod and can be applied to predict the cardiovascular effects of other S1P receptor agonists with different selectivity profiles in rats. Ultimately, it may constitute a basis for prediction of cardiovascular effects of S1P receptor agonists in humans Show less
In the first of this thesis, results are summarized of a randomised crossover trial on the effects of aspirin on markers of inflammation, coagulation and number of endothelial progenitor cells in... Show moreIn the first of this thesis, results are summarized of a randomised crossover trial on the effects of aspirin on markers of inflammation, coagulation and number of endothelial progenitor cells in type 2 diabetic patients without cardiovascular disease. In the second part, results of two systematic reviews on prevalence and clinical relevance of aspirin resistance are reported. Furthermore, we describe time-dependent mechanisms by which aspirin may reduce bloodpressure. Show less
