Modelling in hypertension:From basic physiology to advanced epidemiology

Abstract

A persistently elevated blood pressure (BP), or hypertension, is the most important preventable risk factor for cardiovascular disease and premature death both in the Netherlands and worldwide. The overall aim of this thesis is to apply different modelling strategies to the clinical problem of hypertension, using the combination of physiological and epidemiological approaches. Part 1 focusses on the relation between renal perfusion and hypertension. We develop an adapted Windkessel model to estimate glomerular pressure from intra-renal pressure and flow measurements, and use this model to analyse the effect of static handgrip exercise on renal perfusion. Next, we analyse the relation between BP-lowering, renal function and clinical outcomes using a post-hoc analysis of the SPRINT and ACCORD trials. In the second part, we investigate potential contributing factors that are associated with hypertension and may influence management, including the contribution of sympathetic nervous system activity, forward and backward wave reflections and gut microbiome composition using data from the ongoing HEalthy LIfe in an Urban Setting (HELIUS) multi-ethnic cohort study, which prospectively follows 24000 participants from the six major ethnic groups living in and around Amsterdam. This enables better phenotyping of the individual patient with hypertension and provides new markers and possible therapeutic targets for further studies aimed at improving hypertension management