With ageing populations, the prevalence of age-related disorders such as dementia is on the rise. As there is currently no curable treatment for dementia, the vascular component of dementia is... Show moreWith ageing populations, the prevalence of age-related disorders such as dementia is on the rise. As there is currently no curable treatment for dementia, the vascular component of dementia is increasingly recognised as a key modifiable cause. This thesis aims to investigate biological pathways between risk factors of cardiometabolic disease and cognitive function, in a population of older adults at increased risk of cardiovascular disease (CVD). We hypothesise that changes in physiological functioning caused by (sub)clinical CVD are possible mediators within the pathway leading to cognitive dysfunction. In the first part of this thesis, we studied electrocardiogram-based intervals and serum cardiac biomarkers (such as troponin) in relation to cognitive function. In the second part of this thesis, we studied the interplay of body mass index and serum leptin, loss of body weight and body weight variability, as well as metabolomics-based health scores in relation to cognitive function. We found that various cardiometabolic risk factors are associated with worse cognitive function. The results of this thesis strongly suggest that subclinical changes in cardiometabolic health may exist before cognitive dysfunction becomes apparent. Treating these cardiometabolic risk factors may be of benefit to future cognitive health. Show less
Many biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance... Show moreMany biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance characteristics or fail to meet regulatory standards for approval. Despite their potential, new technologies have added to the complexities of successful translation into clinical practice. Biomarker discovery and implementation require a standardized approach that includes: identification of a clinical need; identification of a valid surrogate biomarker, stepwise assay refinement, demonstration of superiority over current standard-of-care; development and understanding of a clinical pathway; and demonstration of real-world performance. Successful biomarkers should improve efficacy or safety of treatment, while being practical at a realistic cost. Everyone involved in cardiovascular healthcare, including researchers, clinicians, and industry partners, are important stakeholders in facilitating the development and implementation of biomarkers. This article provides suggestions for a development pathway for new biomarkers, discusses regulatory issues and challenges, and suggestions for accelerating the pathway to improve patient outcomes. Real-life examples of successful biomarkers-high-sensitivity cardiac troponin, T2* cardiovascular magnetic resonance imaging, and echocardiography are used to illustrate the value of a standardized development pathway in the translation of concepts into routine clinical practice. Show less
Aim of this thesis was to evaluate contemporary care and prognosis for patients with acute coronary syndrome and identify pitfalls in its treatment. Complications after coronary stent implantation... Show moreAim of this thesis was to evaluate contemporary care and prognosis for patients with acute coronary syndrome and identify pitfalls in its treatment. Complications after coronary stent implantation were explored and demonstrated that in sirolimus-eluting stents, the benefit of reduced repeat revascularization during one year after primary PCI was not sustained during long-term follow-up. Additionally, an increased risk of very late stent thrombosis was suggested. Late stent malapposition, more commonly observed after this stent type and suspected to be involved in the multifactorial etiology of stent thrombosis, is shown to persist in the greater portion of STEMI patients during long-term follow-up, depending on the degree of vessel wall remodelling and change in plaque burden. Women were identified as a sub-population with poorer prognosis early after STEMI. Identification of high-risk patients, and estimation of infarct size and prognosis, which a single measurement of troponin already may indicate, facilitates individualized treatment and likely results in better outcomes. Although numerous novel treatment modalities emerged in recent years, certain pitfalls become increasingly important. Major bleeding is one of them, responsible for an excess mortality amongst STEMI patients after primary PCI, and should be incorporated in risk stratification models for the choice of treatment strategy. Show less
Laarse, A. van der; Cobbaert, C.M.; Gorgels, A.P.M.; Swenne, C.A. 2013
To improve patient outcome, point-of-care (POC) cardiac troponin I/T (cTn I/T) tests applied in a prehospital setting and/or emergency department might play a role as a substitute for central... Show moreTo improve patient outcome, point-of-care (POC) cardiac troponin I/T (cTn I/T) tests applied in a prehospital setting and/or emergency department might play a role as a substitute for central hospital laboratory high-sensitivity (hs) cTn I/T testing if their analytical and clinical performance are equivalent to central hospital laboratory hs cTn I/T tests and if they fulfill an unmet clinical need in the diagnostic work-up of patients with acute coronary syndrome (ACS). To date, current point-of-care (POC) cTn I/T tests are not yet sufficiently analytically sensitive and do not provide accurate and precise values in the reference range nor at the 99th percentile of a healthy reference population. Awaiting the development of improved hs POC cTn I/T tests, current POC cTn I/T tests should be combined with ECG as it takes several hours to detect a rise of cTn I/T in the circulation whereas ischemia-induced ECG changes may be observed soon after onset of chest pain. Although patients with acute ST-segment elevation myocardial infarction (STEMI) are generally diagnosed by ischemic symptoms and ECG only, hospitalized patients with non-STEMI and unstable angina pectoris (UAP) should preferentially be tested with ECG and central hospital laboratory hs cTn I/T tests unless the ECG has already demonstrated diagnostic changes. More evidence and future trials are needed to find out whether in patients with NSTE ACS hs cTn I/T tests should be combined with other tests, such as a test of B-type natriuretic peptide or NT-proBNP. Show less
