Title: Uncovering Contributors to Hypertension through Experimental and Computational Simulation (CHECS)
Funder: Engineering and Physical Sciences Research Council

Abstract: High blood pressure, or hypertension, is one of the most important causes of global morbidity and mortality in the developed world [1]. It has been shown that hypertensive people have a high risk of stroke, heart attack, heart failure and renal failure. The Health Survey for England in 2006 demonstrated that the prevalence of hypertension in the UK increased from 17% in the age group 40-49 years to 77% in those aged 70-79 years [2]. Hypertensive patients are usually identified by a threshold diagnosis of their systolic or diastolic pressures exceeding 140 or 90 mmHg respectively. However this diagnosis tends to misdiagnose the individuals in the large population in and around the threshold making the selection for appropriate therapy difficult. For example one important determinant of hypertension is the flexibility of the aorta (the first artery leading from the heart), which becomes stiffer with age and arteriosclerosis. However, such "stiffness" is only one among other geometrical and mechanical factors that influence the pressure pulse and thus hypertension. Therefore, non-invasive measurement of pulse pressure waveforms has been of interest for more than 100 years, and includes tonometry, Ultrasound and Magnetic Resonance Imaging (MRI). Although the non-invasive measurement of waveforms has become fast, the current analysis of the measured waveform data is relatively simplistic. In particular, the analysis of certain waveform features are performed in isolation and are impeded by a lack of understanding of the relative contributions from arterial stiffness/geometry, wave reflection and ventricular/arterial interaction to hypertensive pressure. Over the last two decades, computational modelling has been established as a new discipline to study the interaction of different parameters in the cardiovascular system. These models can help to separate the various contributions to the pressure waveform and elucidate complex interaction of parameters affecting hypertension. More recently, imaging data of the patient's anatomy and physiology has been introduced in numerical simulations to produce patient-specific models. Although, different models have been developed to investigate the influence of geometrical and mechanical factors, a model validation remains challenging since it would require large studies in animals and patients. This proposal aims at the identification of high-risk individuals by determining the mechanical factors which cause their pressure to be pathological. This approach would allow a better selection of appropriate treatments for the individual patient. For this, we propose the construction of a comprehensive experimental arterial model with which to determine and quantify main contributors to hypertensive pressure as well as to validate our existing computational arterial simulation frameworks (1D and 3D). Translation of these technologies towards the clinic will be facilitated with the construction of full-scale silicone arterial model, which will experimentally simulate haemodynamics of a hypertensive patient dataset. This will be followed by a clinical validation of a computational analysis tools in volunteers and a small patient cohort. References: [1] MacMahon, S., et al.: Blood-pressure-related disease is a global healthy priority. Lancet, 2006. 371: p. 1480-1482. [2] NHS, Health survey for england 2006 latest trends. 2008: Leeds.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR