Project 7

Macrovascular and microvascular aspects of target organ damage in hypertension

Hypertension is associated with structural and functional vascular changes. The cross-talk between macro- and microvasculature is thought to be a key factor in the development of hypertension-related organ damage but remains incompletely understood. In clinical practice, blood pressure load is correlated with observed target organ damage in many patients but long periods of high blood pressure with no or only limited target organ damage have also been observed. Conversely, we also see patients who despite normal or only mildly raised blood pressure have a disproportionally high degree of organ damage. We propose that either 1) a discrepancy in function and structure of the micro- and macrovasculature; or 2) adherence to lifestyle measures and overlooked risk factors such as sleep quality and duration could explain these findings. We hypothesise that hypertensive patients without significant organ damage are characterised by factors that protect the microvasculature, including a globally healthier lifestyle.

The ESR will recruit patients with primary hypertension and a wide range of blood pressures. Within this cohort we will focus on those patients with disproportionate macrovascular damage in relation to their blood pressure level. The ESR will conduct comprehensive characterisation of macrovascular structure and function (pulse wave velocity, ankle-brachial index, carotid intima-media thickness, aortic distensibility by MRI. Assessments of microvascular function and structure will use a range of non-invasive and invasive techniques including cardiac, renal and cerebral MRI to study the coronary microcirculation, renal perfusion and the cerebral microvasculature; retinal imaging. The ESR will assess the interaction between micro- and macro-circulation, by wave separation and intensity analysis; conduct biomarkers studies into cytokine profiles, RAAS system fingerprint, miR profiles and other omics approaches; and lead the non-intrusive assessment of sleep parameters and adherence to healthy lifestyle through connected devices.

Planned secondments include: A secondment with the Boutouyrie lab at the University of Paris, France; a secondment with the Stehouwer/Greevenbroek/Houben group at Maastricht University, Netherlands; a secondment at Microlife, Switzerland, to learn about pulse waveform analysis; and a secondment at Withings, France, to learn how to process, analyse and interpret the data acquired by the connected devices used in the study.