Assessment of sodium and fluid homeostasis as a stratifier and biomarker in hypertension

Abstract

Hypertension is a leading risk factor for mortality and morbidity throughout the world. Despite the availability of pharmacological treatment, a substantial proportion of affected patients do not achieve an optimal blood pressure control which increases their cardiovascular risk. From a pathophysiological perspective, hypertension can be initiated and sustained by retention of body sodium and water leading to a volume overloaded state which is thought to be more common in individuals of African ancestry. Those individuals often display the so-called phenotype of low-renin primary hypertension and tend to have a greater response to diuretic therapy compared to inhibitors of the renin-angiotensin-aldosterone system.

A suppressed plasma renin concentration/plasma renin activity (PRA) is thought to be a biomarker of sodium/volume overload and in some studies has been shown to predict the response to diuretics. However, PRA is influenced by other factors, and cannot be used in isolation to predict in a single individual the response to a specific treatment and the dose titration or selection of class of diuretic.

The objective of this thesis is to examine the potential value of PRA and biophysical markers of sodium and fluid homeostasis: bioelectrical impedance analysis (BIA) and echocardiographic measures of intra-vascular blood volume (EBV). Finally, a novel test that examines the sensitivity of cell membranes to damage by sodium is examined.

The work in this thesis involves:

1. A systematic review/meta-analysis of the change in PRA before & after treatment with different diuretics used in randomized controlled trials (RCT) to assess whether this is sustained over time and whether it varies according to class of diuretic in primary hypertension.

2. The usefulness of bioimpedance and echocardiographic measures of intra- vascular blood volume to detect experimentally-induced acute changes in intravascular volume in primary hypertension.

3. Examining changes in bioimpedance and echocardiographic measures of intravascular blood volume after chronic diuretic treatment in primary hypertension.

4. Examination of a test of the erythrocyte cell membrane sensitivity to damage by sodium and its relationship to PRA and albumin-creatinine ratio as a sensitive measure of target organ damage in a multi-ethnic cohort of patients with primary hypertension.

Date of Award	1 May 2022
Original language	English
Awarding Institution	King's College London
Supervisor	Philip Chowienczyk (Supervisor)