Hypertension & circulation
Professor N Chaturvedi, Professor
Dr Darrel Francis, Senior Lecturer
Professor Alun D Hughes, Professor
Dr Jamil Mayet, Consultant
Professor Simon A McG Thom MD FRCP, Professor
The Hypertension & Circulation group undertakes a wide range of studies that explore the origins and consequences of CVD. The scope of these studies is wide, ranging from laboratory studies of the cells that make up the blood vessel wall to clinical studies in patients - a truly translational ‘bench to bedside’ approach.
The Heart and Large Arteries
The group has a major interest in the assessment of heart and circulatory function in the context of hypertension, diabetes, ethnicity and heart failure. In addition to conventional means of assessment such as echocardiography, arterial ultrasound or measurement of heart rate variability, we have developed and applied novel methods of assessment of the cardiovascular system in man based on the combination of imaging and computational techniques. For example, together with colleagues in Chemical Engineering, Physiological flow studies unit and Imaging Sciences, Imperial College and the Cardiovascular Magnetic Resonance Unit at the Royal Brompton Hospital, we have used computational methods to assess blood flow patterns in arteries in man (image). These studies provide much more information than conventional assessments performed using ultrasound or magnetic resonance imaging. This approach has major potential for identifying haemodynamic determinants of atherosclerosis and exploring the impact of both risk factors and therapies and we hope shortly to use these techniques to visualize blood flow patterns in the coronary arteries that supply the heart.
Together with the Dublin ASCOT centre we have also collected cardiac and arterial measurements on 1100 patients with parallel metabolic and genetic blood samples. This forms a considerable database with extensive characteristics for further interrogation.
The group also has a major interest in ethnic differences in cardiovascular disease. A recent study has examined difference in regional atherosclerosis in European and South Asian subjects. People of South Asian origin are at high risk of ischaemic heart disease but we have shown that for similar levels of coronary disease that levels of lower limb atherosclerosis are lower in South Asian subjects. Reason for these differences will be explored in future studies.
The microvasculature, endothelium and smooth muscle
Abnormalities of the microvasculature (small blood vessels with diameters from 50-100mm) are increasingly recognised as playing a key role in CVD and target organ damage. A number of ways of assessing microvascular function are used, including measurement of skin blood flow using laser Doppler, pharmacological examination of small arteries removed from skin biopsies, or examination of the blood vessels at the back of the eye (the retina). The study of retinal arteries is particularly interesting in view of its potential for use on a population scale. The blood vessels of retina are relatively easy to photograph and provide an insight into the blood supply of the eye and the brain.
Example of semi-automated segmentation. The left panel shows a red-free image of the retina; the right panel shows segmented arterioles (in red) and venules (in blue)
We have developed novel approaches to automate the process of retinal image analysis in collaboration with colleagues in the Bioengineering group at Imperial College (image) that provide quantitative information regarding abnormalities of the retinal blood vessels. These studies have identified important relationships between abnormalities of retinal blood vessels and cardiovascular risk factors and are currently being used in several large international studies. In the long term we believe this approach promises a simple means of early identification of individuals at high level of cardiovascular risk.
In collaboration with the Aga Khan University we are undertaking a study supported by the Wellcome Trust to evaluate interventions for hypertension and retinopathy in Pakistan. This extends research on retinal vascular geometry and cardiovascular disease in collaboration with the University of Wisconsin that has also been funded by the Wellcome Trust. Similar joint projects are underway with Odense University, Royal College of Surgeons Dublin and Edinburgh University – the later being an ambitious venture to explore genetic determinants of cardiovascular structure and function in the people of the Orkneys. The group is coordinating microcirculation investigations in several international large scale intervention trials – DIRECT, ADVANCE & ASCOT The DIabetic REtinopathy Candesartan Trial (DIRECT) is an intervention trial evaluating the inhibition of angiotensin AT1 receptors on the development or progression of diabetic eye disease (retinopathy). The trial involves 320 centres in 27 countries and has recruited a total of 5300 patients.
Basic science studies have focused on the muscular cells that form the walls of blood vessels (vascular smooth muscle cells). These cells are responsible for the narrowing of blood vessels that is a feature of hypertension, atherosclerosis and diabetes.
Imaging of intracellular calcium in a small mesenteric artery using confocal microscopy (a collaboration with C Aalkjaer & H Nilsson Århus)
Current research is examining the mechanisms responsible for the entry of calcium ions into vascular smooth muscle cells. Entry of calcium is the crucial process responsible for arterial narrowing in hypertension and atherosclerosis and we are looking at how novel and established therapies affect this process. Other studies have begun to examine the role of the primitive blood cells that act as precursors of endothelial cells (the cells that line blood vessels) in coronary artery disease and their potential for developing tissue engineered blood vessels. Recent collaborations with visiting researchers from Nijmegen (Netherlands) and Århus (Denmark) have investigated the effect of hypoxia on calcium signalling in vascular smooth muscle cells and possible novel therapeutic strategies for the treatment of septic shock respectively.
