PhDSignificant cardiovascular morbidity and mortality exists in chronic obstructive
pulmonary disease independent of traditional risk factors. A number of different
hypotheses exist to explain this association including the contribution arterial stiffness
and lung hyperinflation.
Non-invasive cardiovascular imaging and assessment are ideal methods through
which this relationship can be further studied although a number of the techniques
have yet to be validated in COPD. In this thesis we aimed to achieve a number of
goals. First, we aimed to assess the reproducibility and level of agreement between
different measures of arterial stiffness in stable hyperinflated COPD. Second, we
hoped to establish the utility of 3 different measurement techniques for measuring
intrinsic cardiac function in stable hyperinflated COPD. Third, in a case-control study
we compared surrogates of cardiovascular risk in hyperinflated COPD patients and a
group matched for cardiovascular risk with normal lung function. Finally, we sought
to understand the impact of pharmacologically reducing lung hyperinflation on
cardiovascular structure, function and arterial stiffness.
We have firstly demonstrated that non-invasive measures of arterial stiffness are
reproducible in stable hyperinflated COPD. Secondly, we have established the level
of agreement and reproducibility of three different CMR techniques for measuring
intrinsic myocardial function which will provide important information for the powering
of future CMR studies in COPD. Thirdly, we have shown that surrogates for
cardiovascular outcomes are adversely affected in COPD compared to a group
matched for global cardiovascular risk, suggesting that current scoring systems may
be suboptimal in risk prediction in COPD. Finally, we have demonstrated that
pharmacological lung deflation has consistent and physiologically plausible beneficial
effects on cardiac structure, function and the pulmonary vasculature. Whether
intrinsic myocardial function can be modulated through prolonged periods of lung
deflation is as yet unverified and should be the focus of future clinical trials.GlaxoSmithKline
Bart’s Charity Special Purpose Fund
