PhD Theses.Background: Cardiovascular disease remains the biggest cause of mortality and morbidity
worldwide. New aetiological models for chronic non-communicable conditions, such as
cardiovascular disease, propose a more extensive and complex network of interconnected disease
determinants than is suggested by traditional risk factor models. Understanding novel disease
determinants and their interactions across different organ systems may be key in alleviating the global
burden of cardiovascular disease. The UK Biobank comprises comprehensive characterisation of
demographics, lifestyle, and clinical status for over half a million participants along with prospective
tracking of health outcomes and, for a large subset of participants, detailed cardiovascular magnetic
(CMR) imaging. Thus, the UK Biobank provides an ideal platform for investigation of novel
cardiovascular disease determinants.
Methods: We present a series of observational studies investigating the association of several novel
exposures with cardiovascular health in the UK Biobank, with consideration given to exposures acting
across key organ systems (heart, brain, gut, bone) and integrated use of CMR data. Additionally, we
describe and illustrate the utility of CMR radiomics, a novel image analysis technique for deeper
cardiovascular phenotyping. Finally, in light of the coronavirus disease 2019 (COVID-19) pandemic,
we investigate the association of pre-existing CMR phenotypes with incident COVID-19.
Summary of results: Our findings demonstrate associations between cardiovascular health and novel
disease exposures acting across different organ systems. We demonstrate the value of a multi-system
approach to understanding cardiovascular health and the importance of cross-system interactions in
disease occurrence and progression. We further illustrate the utility of large scale CMR data for
epidemiologic research in gaining added insights into such relationships and demonstrate the use of
deeper cardiovascular phenotyping with novel CMR radiomics.
Conclusions: Our findings suggest that the search for such novel disease determinants is worthwhile
and important for improving population burden of cardiovascular diseases
