NIHRDataInsights/HRCSData huggingface dataset:
Title: Validating models of congenital heart defects for use in patient-specific assessment and virtual surgery
Funder: Department of Health (England)

Abstract: Repairing congenital heart disease implies performing complex interventions and using sophisticated devices. A surgeon or a paediatric cardiologist could be aided by computational simulations, whereby a computer can simulate a range of anatomies and defects, anticipating the outcome of a surgical operation yet to be performed or the behaviour of a device yet to be implanted. This study aims to prove the reliability of a computational model of Tetralogy of Fallot, then performing virtual surgery on patient-specific anatomies. In the long term, tailored simulation could be reliably performed to improve treatment of such complex congenital conditions.


Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR
Title: Analysis of Recurrent Events in Clinical Trials
Funder: Department of Health (England)

Abstract: Composite endpoints are commonly used as a primary outcome in clinical trials. They increase statistical power and combine multiple outcomes into one. Heart failure is characterised by recurrent hospitalisations, yet composite endpoints usually only analyse the first. We shall develop models for recurrent hospitalisations, noting an association between heart failure hospitalisations and an elevated risk of death, and apply them to data from major trials. Joint frailty methods model the recurrent event process and mortality. Trialists, companies and regulators are receptive to this innovation, which has scope to change statistical practice in trials of heart failure and other chronic conditions.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CARDIOVASCULAR
Title: The impact of frailty on blood pressure lowering treatment and of blood pressure lowering treatment on frailty in those aged over 80 years
Funder: The Dunhill Medical Trust

Abstract: The results of the double blind placebo controlled Hypertension in the Very Elderly Trial(HYVET) changed guidelines to support antihypertensive treatment in those aged 80 and over. Clinicians have raised concerns that the risk/benefit profile may be less favourable in frailer individuals. Although healthy octogenarians were over represented in HYVET the self and investigator reported comorbidities (collected in 70% of the 3845 participants) demonstrate a range of baseline frailty. We intend to utilize this data to derive individual frailty scores enabling us to assess the impact of baseline frailty on trial treatment outcomes. Secondly, analyses will be carried out (using a stochastic dynamic model) to assess whether trial treatment (active/placebo) impacted on frailty over 2 years of follow up (equivalent to mean follow up in HYVET). It is hypothesized that treatment benefit will be seen across the frailty spectrum. The results will further inform treatment policy within the very elderly population.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE;6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Multi-modality imaging to determine the contribution of calcification and inflammation in lower limb arterial disease. A proof of principal study using FDG and NaF PET/CT imaging
Funder: The Dunhill Medical Trust

Abstract: Peripheral arterial disease (PAD) is common affecting > of 5% of the male population over the age of 65 years. It is associated with significant morbidity / mortality which is mainly cardiovascular-related with limb related symptoms progressing affecting in 25% patients. Arterial inflammation and calcification are key processes involved in atherosclerotic disease progression. Anatomical imaging (angiography) cannot measure inflammation . Non-invasive imaging techniques (PET CT) have been developed to detect arterial inflammation using tracers that locate to areas of inflammation (18F-FDG) and active calcification (18F NaF). These have been investigated within the coronary and carotid circulation and have been shown to be a marker of culprit atherosclerotic lesion as well as having the ability to track the effects of anti-inflammatory therapies. The lower limb arterial tree has yet to be investigated with such techniques and this studies aims to provide proof that such imaging techniques are equally applicable.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Evaluating the social and healthcare impact of the Project Sir Gar workplace lifestyle intervention programme.
Funder: Division for Social Care and Health Research (Wales)

Abstract: Cardiovascular disease is the leading cause of premature death in the United Kingdom and includes coronary heart disease, stroke, diabetes and kidney disease. Evidence shows that it is possible to identify the risk factors for these diseases and early intervention to reduce risk can prevent, delay, and, in some circumstances, reverse the onset of disease. This project aims to evaluate the social and health care impact of a lifestyle intervention scheme aimed at the prevention and early identification of cardiovascular and type 2 diabetes risks in the workplace of major employers (Corus, Hwyel Dda, and Carmarthenshire Local Authority) in the Carmarthenshire (Sir Gar) region. Specifically, interviews and focus groups will be conducted across the duration of the project with scheme participants, scheme deliverers, employers, and local health board managers in order to capture the experiences of the key agencies and stakeholders directly involved in, and, affected by the scheme. It is expected that the findings will provide a number of important recommendations for the potential organisation, management and delivery of local authority workplace lifestyle interventions in Sir Gar and across Wales.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: CARDIOVASCULAR
Title: Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction) (update)
Funder: Department of Health (England)

Abstract: Venous thromboembolism (VTE) with an annual incidence of 1 per 1000 individuals is one of the most important preventable causes of morbidity and mortality in hospital patients. VTE has been extensively studied in surgical patients. The benefit of thromboprophylaxis is now generally accepted in surgical patients but medical patients make up the greater proportion of the hospital population. Medical patients differ from surgical patients with regard to their health and the pathogenesis of thromboembolism and the impact that preventative measures can have. The extensive experience from thromboprophylaxis studies in surgical patients is therefore not necessarily applicable to non-surgical patients.The current review aims to determine the effectiveness and safety of heparin thromboprophylaxis in patients admitted to hospital with an acute medical illness.The current review is now out of date and at least a further 15 studies are to be considered for inclusion. Access statistics have shown this review to be consistently in the top 20 of our most access reviews and the editorial base have been contacted by numerous people asking for the status of this review indicating it is a critical issue in their institution. A timely update of this review is now warranted.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CARDIOVASCULAR
Title: Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus conventional surgery for great saphenous vein varices (update)
Funder: Department of Health (England)

Abstract: In 2009/10 35659 varicose veins procedures were carried out in the NHS indicating a considerable financial cost. Varicose veins are dilated tortuous superficial veins. They are conventionally treated with surgery to remove the veins by stripping them to the level of the knee. New less invasive treatments seal the main leaking vein in the thigh using laser (endovenous laser therapy) radiofrequency ablation (RFA) or foam sclerotherapy. These techniques may result in less pain after the procedure fewer complications and a quicker return to work and normal activities with improved patient quality of life as well as avoiding the need for a general anaesthetic. NICE guidelines currently recommend the use of endothermal ablation (guideline-specific combined term for endovenous laser therapy and RFA) over foam sclerotherapy and surgery. However this guidance acknowledged a lack of high quality evidence on any clinical difference in critical outcomes between endothermal ablation or foam sclerotherapy over conventional surgery and called for further research in this area.Further large studies have been now been published and an update of the Cochrane review on endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus conventional surgery for great saphenous vein varices which addresses this key issue is therefore warranted.


Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: CARDIOVASCULAR
Title: Structure-function studies on proteins implicated in angiogenesis.
Funder: Wellcome Trust

Abstract: Protein molecules adopt different shapes to perform diverse functions within the body. Often they interact with other massive molecules such as another protein/DNA or with small molecules, leading to a cascade of events culminating in a biological function. The study of the shapes of proteins and DNA constitutes the field of structural molecular biology. It is a very powerful and exciting approach to relate shapes of molecules with their biological functions. This provides the basis for understa nding their key role both in normal bodily functions and aberrant conditions such as cancer and inflammation amongst others. I am a structural biologist who uses X-ray crystallography to study the three-dimensional shape of biological molecules such as proteins and DNA. We are one of the few groups studying 3D structures of some key molecules involved in angiogenesis with a view to understanding their function. The process of angiogenesis involves formation of new blood vessels which is critical for both embryonic development and a variety of normal postnatal physiological processes. Various pathological processes, most notably tumour growth and chronic inflammation are also known to be dependent on the new vessel formation. Hence a comprehensive understanding of the process at the molecular level is vital.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CARDIOVASCULAR
Title: Mechanisms of cardiovascular pleiotropy and buffering in Cited2 deficiency.
Funder: Wellcome Trust

Abstract: Congenital heart disease (CHD) is a major cause of disability and death. Some types are more severe than others. We have identified a gene (CITED2) that when mutated - in mice and in humans - gives rise to many different types of heart defect. This is called pleiotropy: Greek for many turnings , and is important as some heart defects have much worse outcomes than others. In inbred mouse strains these heart defects occur in all mutants, whereas in F1-hybrids the frequency is much reduced, i.e. the mutation is buffered by hybrid vigour. Likewise, CHD patients with CITED2 mutation can inherit it from parents who are entirely normal. The burning question is: why does CITED2 mutation not result in cardiac malformation on certain occasions? To paraphrase Sherlock Holmes, this is a curious incident, akin to the one where the dog did nothing in the night-time. I believe that solving this riddle will allow us to identify mechanisms that prevent or reduce the severity of CHD in the face of an underlying genetic defect. Such mechanisms could be targeted in pregnant mothers - analogous to the use of folate to prevent congenital defects such as spina bifida.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Integrated functions of TRP channels in vascular smooth musccle cells.
Funder: Wellcome Trust

Abstract: Blood vessels are essential for life in many animals, allowing flow of nutrients to tissues and removal of waste products. They play critical roles in maintaining correct blood pressure and develop, adapt and survive according to the needs of the animal. Blood vessels also have roles in major causes of death and disability: New blood vessels enable expansion of malignant tumours, where as abnormalities in blood vessels (resulting in occlusions or leaks) are the cause of many cases of heart attack, stroke and amputation. We want to advance understanding of blood vessels by conducting research into a major cell type within them, the smooth muscle cell. This cell retains remarkable ability to


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CARDIOVASCULAR
Title: Complement-mediated endothelial cell injury and cytoprotection: relevance to the pathogenesis and treatment of atypical HUS.
Funder: Wellcome Trust

Abstract: Kidney failure has many different causes. An important way in which the kidneys can be damaged is by an injury to the cells which line the blood vessels within the kidney. If this injury is severe then the kidneys cannot recover their function. Kidney dialysis and/or transplantation are then needed. Haemolytic uremic syndrome (HUS) is one cause of this type of injury. In severe cases, this condition can run in families. It can also recur in kidney transplants, causing them to fail. Some fam ilies have a change in a gene which normally codes for a protein that protects our bodies from infection. Occasionally these proteins can be missing or mutated so that we are unable to protect our blood vessels properly. In our work, we will add these mutated proteins to blood vessel cells grown in culture to see how the damage to kidney blood vessels is caused. We will also look at the kidneys in a mouse model of this condition which has the mutated protein in its blood stream. This informat ion will be used to develop a safe and effective drug treatment to treat human patients who develop HUS and who need kidney transplants.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Higher resolution cardiovascular epidemiology: unique insights from linking the national cardiac event register with primary care records and highly phenotyped cohorts.
Funder: Wellcome Trust

Abstract: Different types of heart disease, including a spectrum of angina and heart attacks, are diagnosed by clinicians, and details recorded in separate electronic records. What is not known is whether these different forms have different causes at the population level. This uncertainty motivates our three aims: Aim I We seek to link the clinical details in the Myocardial Infarction National Audit Project and the primary care record (using the General Practice Research Database), and existing coho rt studies which are part of the UCL genetics consortium. This resource, including about 80,000 linked cases of specific forms of heart disease, will be carefully checked and validated and then made available to the wider research community. The size and clinical detail of this resource has no parallel internationally. Aim II We will find out the extent to which different risk factors predict the onset and progression of this spectrum of angina and heart attack. We will exploit linkages in the electronic patient record to examine the role of the social environment, psychosocial factors, the physical environment, inflammation, and widely measured blood markers. Aim III We will set up new training opportunities, including short courses, Masters and PhDs, to increase research using such data.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Modulation of Vasomotor Tone by Hypoxia in the Pulmonary Circulation.
Funder: Wellcome Trust

Abstract: HPV is a phenomenon found in the pulmonary blood vessels which bring blood to the lungs, where it picks up oxygen. If the flow of air to a part of the lung is blocked it becomes hypoxic (oxygen starved). Blood flow to hypoxic regions of the lung is harmful, because it reduces body oxygen levels. To prevent this wasteful bloodflow to hypoxic lung regions, the body employs HPV to constrict arteries serving these regions, forcing more blood to lung regions which are not hypoxic. Unfortunately, in diseases such as chronic obstructive airways disease, oxygen levels throughout the lungs may fall, in which case HPV constricts most of the pulmonary arteries. This increases the blood pressure in the lungs, eventually damaging the right side of the heart, which pumps blood through the lungs. It would therefore be useful to these patients if we could prevent HPV. However the processes that maintain HPV remain largely unknown. Based on previous studies, we hypothesise that HPV is caused by the re lease of free radicals in pulmonary blood vessels. We plan to prove this hypothesis by comparing the effects of hypoxia and free radicals on lungs and pulmonary arteries from rats and mice.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: The effect of maternal iron status and intake during pregnancy on cardiovascular disease risk in the offspring.
Funder: Wellcome Trust

Abstract: Obesity and high blood pressure are major risk factors that contribute to premature death from heart disease and stroke. Factors affecting the development of the foetus before birth influence the development of obesity and high blood pressure in adulthood. Mother's diet during pregnancy plays an essential role in foetal development. Diet deficient in essential nutrients, including iron, is still a common problem even in developed countries. This study assesses the direct relationship between iro n storage in the mothers body during pregnancy and blood pressure and obesity in their offspring. Many studies have shown that obesity and high blood pressure are also more likely to develop in people born with low birthweight. Therefore, this study also assesses the effect of iron intake by the mother during pregnancy on birthweight and other outcomes in the newborn. The study will involve using information collected from the mothers during pregnancy regarding diet and supplements int ake. Their body iron will be measured. The offspring of women with genetically higher iron body stores will have their weight and blood pressure measured. The results of the project will determine whether increasing iron intake in the diet during pregnancy has any long term health effects on the offspring.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Signalling circuitry controlling hyperpolarization and dilatation in resistance arteries.
Funder: Wellcome Trust

Abstract: Arteries are the body s active plumbing, changing diameter to distribute blood. As well as ensuring blood flow adequately supplies cell nutrients, diameter controls resistance across the vasculature helping to determine blood pressure. Changes in diameter reflect contraction and relaxation of very small smooth muscle cells that wrap round to form the artery tubes . The muscle cells are influenced by a thin lining layer of endothelial cells in contact with the blood, and by nerves round th e outside. Recent research, including our own, has found that normally endothelial cells continually decrease blood pressure by relaxing the smooth muscle through hyperpolarization . Hyperpolarization reflects the opening of small protein-lined pores in the membranes encasing endothelial cells, that is then transferred to the muscle by chemicals and physical connections (called gap-junctions). Cardiovascular disease compromises this influence, so the muscle contracts increasing resistance an d blood pressure to cause hypertension and other serious events, such as stroke and heart attack. Our planned research will show how hyperpolarization in endothelial cells is integrated to regulate diameter up and down the length of arteries, thus controlling blood pressure and flow in our bodies, and indicating new ways to treat high blood pressure and prevent stroke and heart attack.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CARDIOVASCULAR
Title: Functional compartmentation of betaAR cAMP/Ca2+ signalling to surface structures of normal and failing cardiac myocytes investigated by the nanoscale SCIM/FRET'smart' patch technique.
Funder: Wellcome Trust

Abstract: Adrenaline controls the force and rate of contraction of the heart by its effects on molecules within the cell. It is thought that this is aided by the spatial relationship between adrenaline receptors (bARs) and specialised regions of the heart muscle cell surface. With a new microscope developed in our laboratory we can scan the surface of the living cell and identify these regions, with an accuracy that was not possible before. We will then use new chemical probes which give a light signal when the molecules in the cell are increased, to see whether this happens more strongly in the specialised region. Electrical signals can also be recorded from these areas. We know that the surface of the cell is disrupted by heart failure, and we can examine the effect of this on bAR location. Heart failure leads to greater numbers of arrhythmias or more cell death in response to adrenaline, and we will look at the link between bAR movement and these changes. Our work will focus on basic mech anisms in heart failure, but is also relevant for the design and use of drugs since many of the compounds used in these patients are aimed at modulating bARs.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Role of Regulator of G protein Signalling 1 (RGS1) in Inflammatory Cell Recruitment and Plaque Formation in Atherosclerosis.
Funder: Wellcome Trust

Abstract: Atherosclerosis, the underlying cause of angina, heart attacks and stroke, is associated with the development of inflammation in the blood vessel wall. Inflammatory cells are attracted to areas of atherosclerosis by molecules known as chemokines. We have identified a new molecule, RGS1, that is found at high levels in atherosclerosis. In other types of inflammation RGS1 appears to be a critical controller of the response of inflammatory cells to chemokines. We now propose to investigate the impo rtance of RGS1 in the development of atherosclerosis and its impact on the constituents of atherosclerotic plaques that confer risk of heart attack or stroke. Understanding the function of RGS1 may allow the development of new therapies to reduce the progression of atherosclerosis and reduce the likelihood of heart attack or stroke.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR