Association of markers of intravascular volume and fluid homeostasis with cardiac remodelling and cardiovascular function in hypertension

Student thesis: Doctoral ThesisDoctor of Philosophy


Hypertension (HT) is the most important cause of morbidity and mortality because of major adverse cardiovascular events such as stroke, myocardial infarction, and heart failure. Retention of sodium and water are thought to underlie an increased circulating intra-vascular volume that contributes to the pathophysiology of HT as well as the development of adverse cardiac remodelling, a mechanism that may be more important in individuals of African heritage compared to those of European heritage. However, to what extent this mechanism is mediated by genetic or environmental factors is unknown. Secondly the assessment of fluid homeostasis and particularly circulating intra-vascular volume and cardiac pre-load in subjects with HT is challenging.
On the basis of these concepts, the aims of this PhD were: 1) to compare hypertensive individuals of African heritage in two contrasting environments (Africa and the UK) to elucidate potential environmental and genetic causes of sodium retention and cardiac remodelling; 2) to evaluate if changes of cardiac pre-load in subjects with HT could be detected by cardiac ultrasound and to test those indexes during lower limbs venous occlusion (LVO), a novel technique of pre-load reduction and 3) to investigate the acute effects of LVO on cardiovascular function and arterial stiffness. The observational study conducted in Africa and in the UK suggested that environmental differences in sodium/potassium intake may contribute to HT and cardiac remodelling via effects on circulating intra-vascular volume.
Preliminary data obtained in subjects with HT demonstrate that relatively small variations in cardiac pre-load can be detected by studying the inferior vena cava diameter and super vena cava peak flow velocities by a conventional transthoracic cardiac ultrasound. The physiology of non-invasive pre-load reduction was investigated in a series of studies involving LVO. The results suggest that pre-load primarily influences the early phase of ventricular contraction and reduces myocardial wall stress, the main stimulus to cardiac remodelling, but also increases vascular stiffness.
Date of Award1 Jul 2021
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorPhilip Chowienczyk (Supervisor) & Andrew Webb (Supervisor)

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