Title Affiliations Abstract "Causes of micro-inflammation and cardiovascular disease in chronic kidney disease: role of uremic peptides" "Department of Internal medicine" "Retention of uremic solutes as well as renal replacement therapy contribute to micro-inflammation related to the cardial burden in chronic kidney disease. Especially the effect of uremic peptides on leukocytes and specific leukocyte subpopulations will be evaluated in an in vitro set-up. The pathophysiological mechanisms involved, will be elucidated, aiming at a classification of the retention solutes according to their toxicity." "Cellular Interactions and Heterogeneity in Ischemic Cardiovascular Disease" "Stefan Janssens" "Cardiology, Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, Cardiovascular Imaging and Dynamics, Cardiac Surgery, Chemistry, Kulak Kortrijk Campus" "Cardiovascular disease, and specifically ischemic heart disease, remains the leading cause of death worldwide. Failure of state-of-the-art therapies emphasizes the need for a better understanding of key pathogenetic events in the evolution of the disease that can lead to early identification of individuals at increased risk and to novel therapeutic strategies reducing acute ischemic damage and remodeling towards heart failure in advanced disease. Several risk factors have been identified that, in early stages of the disease, prime the vessels for atherosclerosis and thrombosis, eventually leading to stenosis and episodes of acute ischemia with myocardial infarction. In advanced disease, additional local modifiers of increased mechanical load and ischemia reinforce deleterious remodeling of the heart. None of these processes can be reduced to a single actor and mechanistic insights require diversified, complementary and integrative approaches. The proposed program introduces a novel concept of cellular heterogeneity where depending on prevailing risk factors and disease modifiers, circulating and resident cells in the arterial vessel wall and in the heart adapt a specific molecular footprint, and consequently functional phenotype, in response to local and systemic cues. By doing so, cells further modulate the cardiovascular phenotype in heterocellular cell-cell interactions that reciprocally reinforce disease progression. The overall aim is to explore mechanisms of early and advanced disease within this conceptual framework, to validate findings in patient biosamples, and to initiate translation into clinical diagnostic and ther apeutic practice." "Non-invasive optical measurement and physical modeling of blood pulse velocity for early detection of cardiovascular disease." "Department of Information technology" "The goals of the current project are: Development of a new contact less method, based on light interferometry which makes use of the Doppler shift of reflected light, which will allow us to measure PWV between two well defined locations close to one another. Designing and building a very compact two-channel laser-Doppler heterodyne interferometer which allows to measure blood PWV in realistic circumstances. Making a physics-based model of the fluid dynamics, and using this model to calculate stiffness of the artery. Explorative research for miniaturization and integration of the interferometer components, as onset for a fully integrated micro-vibrometer." "Proteomics and Metabolomics for Prevention, Diagnosis, and Mechanistic Insights in Cardiovascular Disease" "Zhenyu Zhang" "Hypertension and Cardiovascular Epidemiology" "Cardiovascular disease is multifactorial, which means it is influenced by genetics, behaviors, socioeconomics, and environment. Preventive cardiology by addressing modifiable risk factors has advanced significantly in recent years. Despite the current risk prediction algorithms and intervention strategies, cardiovascular disease remains the leading cause of mortality. Therefore, the use of additional biomarkers is being advocated to improve risk prediction accuracy. Biomarkers based on the proteins in an organism (proteomic biomarkers) or derived from metabolism (metabolomic biomarkers) are useful tools for more accurate phenotyping, reflecting molecular characteristics and enabling personalized interventions. The use of proteomics and metabolomics can thus improve the comprehension of underlying biological mechanisms beyond apparent clinical abnormalities. This PhD thesis aimed to a) investigate proteomic signatures for vascular health and their prognostic value for cardiovascular outcomes in the general population; b) use urinary proteomic biomarkers to screen for long-term complications after heart transplantation and understand the potential disease mechanisms; c) apply metabolomics to study lipid metabolism in upper body obesity and the metabolic changes in individuals seemingly healthy.Blood vessel health (vascular health) gets worse with aging. In this PhD thesis (Chapter I), we studied the urinary proteomic signature for three vascular changes: arterial stiffness, vascular calcification, and coronary atherosclerosis. Arterial stiffness is a hallmark of vascular aging and a known risk factor for cardiovascular disease. Pulse wave velocity is a standard measurement for arterial stiffness. We identified a urinary proteomic profile highly correlated with pulse wave velocity and this may be an alternative approach to quantify arterial stiffness (Chapter I, Part I). The urinary proteomic signature included diverse proteins involved in collagen turnover, cell adhesion, inflammation, and lipid metabolism. The urinary proteomic also had predictive value for cardiovascular disease and mortality.Vascular calcification is a basic pathological change associated with arterial stiffness and atherosclerosis. Matrix Gla protein is an important inhibitor of vascular calcification. Chapter I, Part II found that increased urinary matrix Gla protein correlates with increased risk of overall and cardiovascular mortality. The risk stratification was more accurate when urinary matrix Gla protein was added to the risk calculation. Factors affecting urinary matrix Gla protein excretion were circulating matrix Gla protein (desphospho-uncarboxylated, dp-ucMGP), sex, age, urine microalbumin, smoking, and total cholesterol. Along the same line, the urinary proteomic signature associated with coronary artery disease was studied (Chapter I, Part III). We developed a new proteomic classifier consisting of 160 urinary peptides and validated its predictive value in an independent cohort of 893 participants. This classifier was able to improve the risk classification on top of the known cardiovascular disease prediction formulas (the Framingham risk score and SCORE2). The new proteomic classifier maintained its predictive power for coronary artery disease after accounting for clinical risk factors. Particularly, peptides derived from collagen degradation, inflammatory responses, and lipid metabolism were found to be abundant in our urinary proteomic classifier.We also used urinary proteome analysis to detect two common complications after heart transplantation that can impair the function of the transplanted heart and increases the risk of death (Chapter II). Vasculopathy of the transplanted heart is a progressive thickening of the donor's coronary arteries. Its incidence increases with time after heart transplantation, and screening is completed by invasive coronary artery examination. In Chapter II, Part I, we identified a urinary proteomic signature for the detection of transplanted heart vasculopathy and validated it in an internal cohort. The peptides involved in fibrosis, platelet aggregation, and coagulation might play a role in the development of transplanted heart vasculopathy. The use of anti-rejection medications increases the risk of cancer after heart transplantation. Screening cancer in patients who underwent heart transplantation involves multidisciplinary efforts. Thus, we sought urinary proteomic markers specific to cancer after heart transplantation in Chapter II, Part II. Our findings showed that urinary proteomic analysis can detect cancer patients and distinguish solid organ cancer from skin cancer. The urinary proteomic signature of solid organ cancer was related to collagen degradation, cell adhesion and apoptosis, and tumor formation. Moreover, it was associated with an increased risk of death.In Chapter III, we applied metabolomics to characterize the metabolic changes in obesity. We showed that VLDL particle number is the lipoprotein component most strongly associated with waist-to-hip ratio and that LDL might underestimate the lipid abnormality in people with obesity (Chapter III, Part I). The association between waist-to-hip ratio and VLDL particles was significantly determined by insulin sensitivity. This study highlighted the importance of waist-to-hip ratio and the treatment targeting VLDL particles and insulin sensitivity in abdominal obesity-related dyslipidemia.People with obesity have diverse cardiometabolic risks. In Chapter III, Part II, we conducted a large prospective population-based metabolomic study. We found that there were unfavorable metabolic changes in individuals with metabolically healthy obesity, although their cardiovascular risk might remain low for a short period of time. Our findings supported that early intervention should be recommended for any form of obesity to prevent potential long-term cardiovascular risk.In summary, our findings clearly suggested that urinary proteomic analysis and circulating metabolomic profiling allow molecular phenotyping of cardiovascular disease and additional refinement of risk calculations based on clinical characteristics. These omics signatures can be used to improve the risk stratification of cardiovascular disease, develop new diagnostic tools for detecting complications after heart transplantation, and provide insights into pathological changes that thereby enable the development of personalized treatment strategies. " "Scaling-up Packages of Interventions for Cardiovascular disease prevention in selected sites in Europe and Sub-Saharan Africa: An implementation research (SPICES)" "Hilde Bastiaens" "Global Health Institute (GHI), Epidemiology and social medicine (ESOC), Primary and interdisciplinary care Antwerp (ELIZA)" "The overall research objective of the SPICES project is to implement and evaluate a comprehensive CVD prevention and control program in five settings: a rural & semi-urban community in a low-income country (Uganda), middle income (South Africa) and vulnerable groups in three high-income countries (Belgium, France and United Kingdom) as well as to identify and compare the barriers and facilitators across study contexts. The project will be evaluated using a mix of qualitative and quantitative methods. At the beginning of the project, we will conduct baseline assessments including literature reviews, formative studies, household surveys (where feasible) and learn lessons from other projects to understand healthcare and lifestyle practices, barriers, and facilitators. A costeffectiveness and cost benefit analysis will be included. In addition, the teams will conduct site exchanges visits to learn from each other and organise policy dialogues to ensure sustainability and maximise impact of the interventions." "Analysis of the Effectiveness and Economic Viability of Different Cardiovascular Disease Treatment and Prevention Strategies in Various Subpopulations" "Zhenyu Zhang" "Hypertension and Cardiovascular Epidemiology" "Background Due to advanced antiretroviral therapy (ART), the life expectancy of people living with human immunodeficiency virus [HIV, (PLWH)] is approaching that of the general population, and the burden of comorbidities such as cardiometabolic disorders (CMD) and cardiovascular disease (CVD) are increasing. Apart from the ageing factor, compared with the general population, PLWH have higher risks to develop CMD and CVD due to intravascular inflammation resulting from HIV infection and the adverse effects of ART. This treatment dilemma imposed a hurdle in CMD and CVD management for PLWH. Myocardial strain and strain-rate imaging (deformation imaging) assessed by speckle tracking echocardiography are non-invasive to assess myocardial function. CMD and CVD are long-process chronic diseases. Speckle tracking echocardiography can detect subtle changes in myocardial strain rate; thus, with the values, the clinicians can evaluate early myocardial damage in asymptomatic patients. Using myocardial strain and strain rates to prevent CVD occurrence due to drugs or the diseases per se has been applied in many conditions, e.g., patients with cancer, auto-immune diseases or sepsis. The image results can provide evidence of early myocardial damage and help make various intense preventive strategies for the major adverse cardiovascular events (MACE), i.e., stroke, acute myocardial infarction, heart failure, and cardiovascular death. HIV infection has been viewed as an independent risk factor of CVD, and ART has been shown to relate to CMD. For PLWH, early detection of myocardial injury due to viral infection or adverse effects from ART and optimal prevention before the MACE has become a critical healthcare issue nowadays. However, although speckle tracking echocardiography can benefit CVD prevention, the assessment method is not routinely used for Taiwanese PLWH, mainly due to lacking promising data. Myocardial strain and strain rates are ethnicity-specific, age-specific, disease-specific and medicine-specific, and the data for Taiwanese PLWH are still absent. The association of myocardial strain rates of Taiwanese PLWH and CVD risk factors and HIV-related factors (i.e., CD4 counts, HIV viral loads and ART use) remained unknown. Also, if myocardial strain and strain rates can be used in CVD prevention in PLWH, the cost-effectiveness of strain-targeted cardioprotection by speckle-tracking echocardiogram needs a comprehensive analysis in the Taiwan setting. Therefore, this project will examine the following aims: Aim 1: To examine the HIV-specific myocardial strain rates and investigate the effect of demographic data, CVD risk factors, and HIV-related factors (e.g., CD4 counts and viral loads) on strain rates in PLWH  Aim 2: To examine how the trajectory of myocardial strain and strain rates is related to CMD, HIV-related variables and CVD risk factors in a longitudinal PLWH cohort. Aim 3: To examine the cost-effectiveness of strain-targeted cardioprotection for CVD prevention in PLWH in Taiwan setting. Methods For aim 1: this project will retrospectively identify the PLWH patients who do not have CVD nor malignancy before HIV diagnosis in the Chi Mei HIV Clinical database from 01 July 2017 to 31 December 2017. Likewise, the healthy subjects who do not have HIV infection, CVD, or malignancy will be identified from the Chi Mei Health Examination Database from 01 July 2017 to 31 December 2017. Basic characteristics, CVD risk factors, HIV-related parameters, echocardiographic values and myocardial strain data will be collected and analyzed. Continuous variables will be reported as a mean ± standard deviation (SD), while categorical variables will be presented as percentages. Then, an independent samples t-test or Mann-Whitney U test will be used to compare the continuous variables between two groups; the chi-square or Fischer exact test will be used in categorical variables. Pearson’s correlation analysis will be carried out to examine the association between myocardial strain rates and the variables with normal distribution, whereas Spearman’s correlation analysis will be employed for the variables without normal distribution. A p-value smaller than 0.05 will be considered statistically significant, and all statistical analyses will be performed using SPSS 15 software. For aim 2, a Double V program (HIV and CV) has built a PLWH cohort since 2017. Briefly speaking, patients in the cohort would be followed up regularly, and the data of basic characteristics, laboratory data in terms of CMD, echocardiographic parameters and myocardial strain values were collected at every visit. This project will employ individual-based trajectory modelling to classify the various trends of myocardial strain rate over the six visits from 01 July 2017 to 31 December 2021 in the Double V cohort. Furthermore, a mixed-effect model will be conducted with strain-rate trajectories as the dependent variable to examine how the trajectory is related to the independent variables of CMD and CVD risk factors in PLWH. For aim 3, the project will construct a Markov model using Monte Carlo simulation to assess the cost-effectiveness of strain-targeted cardioprotection in PLWH by projecting the direct lifetime costs and quality-adjusted life-years (QALYs). Since the Taiwanese healthcare insurance system is universal coverage and single national payer, the cost-effectiveness will be analyzed from a single national payer’s perspective. Besides, there has been a lack of consensus on the willing-to-pay threshold, so one- and three-folds of Taiwanese Gross Domestic Product (GDP) per capita in 2021 will be used to be the threshold according to the recommendation of the World Health Organization. Incremental cost-effectiveness ratio (incremental costs / incremental QALYs) against the one-fold and three-fold GDP per capita will be used to determine whether the strain-targeted cardioprotection in PLWH is a very cost-effective or cost-effectiveness strategy from a national payer's perspective in the Taiwan setting. Significance This project will collect and analyze the relevant data from the biggest Asian PLWH cohort receiving a longitudinal examination of speckle tracking echocardiography. The HIV-specific myocardial strain and strain rates in PLWH will be examined with the data, and the effect of different variables on strain rates in PLWH will be estimated. Besides, this project will examine how the trajectory of myocardial strain and strain rates is related to CVD risk factors in a longitudinal PLWH cohort. The results will provide the reference data for strain-targeted cardioprotection in CVD prevention among PLWH. Last, the utility scores will be estimated by analyzing the dynamic change of quality of life in PLWH, and the data will be used in future health economic evaluations. From a national payer's perspective, the cost-effectiveness analysis will provide evidence in policymaking of strain-targeted cardioprotection in CVD prevention among PLWH, and the results may encourage multidisciplinary care with HIV specialists and cardiologists for PLWH. The cost-effectiveness model designed in this project will be applied in future studies in terms of cardiovascular or cardiometabolic prevention among PLWH." "Evolution Of Cardiovascular Disease Research: Quantitative Analyses Of Scientific Publications" "Karin Sipido" "Experimental Cardiology, ECOOM - Centre for Research and Development Monitoring" "Cardiovascular research has underpinned major advances in patient care but the introduction of new therapies has slowed down. Experts in the cardiovascular field are concerned that there is a decline in innovation in cardiovascular research and that fragmentation of this broad field is leading to loss of cross-pollination and missed opportunities for translation of research from bench to bedside. In this context, in this PhD project we examined cardiovascular research publication output over a 20-year period to provide data driven evidence about cardiovascular disease research.The main research questions focused on assessing the change in the strength and structure of communication and collaboration in the cardiovascular field over time.  We also worked to identify and characterise the topics within the cardiovascular field.We used a hybrid text-citation based information retrieval strategy to establish a broad dataset of publications in the cardiovascular field from 1992-2013. We obtained all bibliographic data for 845,701 cardiovascular publications from the Web of Science database, including over 5.8 million citations to these publications. We used quantitative methods, including bibliometrics, network analysis and text mining, to analyze the dataset of cardiovascular publication output.Key findings include that the publication output in cardiovascular research has grown steadily from 1992 to 2013. The number of countries participating in cardiovascular research has increased; however, the geographical distribution of research outputs has changed over time. The share of publications by the USA has decreased, while other countries increased their share of publications. In particular, China experienced a dramatic increase in the number and share of cardiovascular publications. Overall, there was also an increase in international collaborations in cardiovascular research, with more authors from different countries publishing research together. The countries with more international collaborations also had increased visibility, especially if they already had high impact research.The analysis of 565 journals found that cardiovascular research is being published in 104 newly established journals since 1993. Overall, an equal share of cardiovascular documents is published in core cardiovascular journals as in broader biomedical science journals. This is an indicator of the broad range of cardiovascular research taking place and, potentially, of growth in interdisciplinary research. Studying the journal networks we found growth in clinically focused cardiovascular research over time. Some areas in cardiovascular research maintain a stable journal network over time, such as the areas of surgery, anesthesiology and nuclear medicine, as they link more closely with the broader journals in these fields than with basic science or clinical cardiovascular journals. Over time the communication between clinical and basic/preclinical journal networks increases to the point that the two separate communities merge, a potential indicator of translation in cardiovascular research.In the last part of this project, we identified and named, with expert input, 175 topics within the cardiovascular research from 2004-2013. We also used different methods to identify and name the largest ten groups or networks of documents in 2006-2008 and in 2011-2013. The most prevalent topics and largest groups had a large clinical focus and also covered the broad issues of evidence-based guidance, cardiovascular disease risk factors, mortality, biomarkers, cell signalling and gene transcription, among others.This evidence and increased understanding of the variation in cardiovascular research across countries, journals and content, provides added value to the cardiovascular community and its stakeholders when undertaking future decisions in research and policies.   " "Home-based interventions to increase physical activity in patients with cardiovascular disease" "Véronique Cornelissen" "Research Group for Rehabilitation in Internal Disorders, Cardiology" "The changing demographics and deteriorating lifestyle of our era result in an increase in the occurrence of cardiovascular disease, which is neither economically or socially sustainable. Exercise is a cornerstone in the therapy of cardiovascular disease, since a more physically active lifestyle results in a decrease in cardiovascular morbidity and mortality.Center-based cardiovascular rehabilitation is well-implemented in Belgium, however participation rates are low, and long-term adherence to an active lifestyle is extremely poor. Home-based exercise programs, might be a solution for increasing patient adherence and self-management.In this doctoral project, the feasibility and benefit of technology-supported home based exercise programs for patients with cardiovascular disease will be explored and investigated." "Autophagy induction as mechanism of action in cardiovascular disease prevention by olive polyphenols." "Lynn Roth" "Physiopharmacology (PHYSPHAR)" "Atherosclerotic plaque rupture is the leading cause of acute cardiovascular syndromes and is responsible for 3.9 million deaths in Europe every year. Preventive strategies are greatly needed to reduce the health care burden of cardiovascular disease (CVD). The Mediterranean diet results in a lower CVD risk, with virgin olive oil as its key element. Many of the health-promoting effects are ascribed to the olive polyphenols (OPs), which are known to be antioxidants, but recently a link with autophagy induction was shown. Autophagy is a cellular housekeeping mechanism and autophagy deficiency is detrimental in the development of CVD. Thus, inducing autophagy is likely to be an effective preventive strategy. OPs were identified as natural autophagy inducers, but further research is needed to define the contribution of this mechanism to their atheroprotective effects. Therefore, we aim to elucidate the role of endothelial cell autophagy in the atheroprotective properties of OPs. The research objectives are divided in 2 work packages: (1) Selection of the most potent autophagy-inducing OP and the most therapeutically effective dose, (2) Investigation of the atheroprotective effects of an OP and the role of endothelial cell autophagy. This project will give insight in the mechanism of action of OPs and is an important step towards the implementation of OP nutraceuticals for the prevention of cardiovascular disease." "From hit to lead: inducing basal autophagy for treating cardiovascular disease." "Pieter-Jan Guns" "Physiopharmacology (PHYSPHAR)" "Autophagy is a normal physiological process that maintains intracellular homeostasis by degrading unnecessary or dysfunctional cellular components in lysosomes. This way, autophagy supports cell survival in unfavourable conditions and represents a reparative and life-sustaining process. Impaired autophagy is increasingly recognized as a hallmark of aging and of multiple human pathological conditions, including cardiovascular disease. Inducing autophagy could be a game-changer in the treatment of cardiovascular disease, but the potential of autophagy inducing drugs has not been realized yet due to the absence of potent and selective tool compounds. The current proposal will start from a number of hits identified in a high-throughput screening and will further validate these lead candidates through a series of in vitro and in vivo studies focussing on vascular biology."