Biomechanical Analysis of Human Coronary Atherosclerotic Plaques in Response to Pharmacotherapy, and in Predicting Adverse Clinical Events

Myocardial infarction, a leading cause of mortality and morbidity worldwide, is often the result of coronary plaque rupture. Previous histological work has demonstrated that ruptured plaques are associated with higher stress, with in vivo intravascular studies linking higher plaque structural stress (PSS) with the presentation of acute coronary syndrome. Endothelial shear stress (ESS) on the other hand has been implicated in early plaque development and plaque growth, suggesting that both PSS and ESS can influence future plaque behaviour. The work presented in this thesis first demonstrates that PSS changes with pharmacotherapy, in particular, high-intensity statin (HIS) treatment prevented the rise in PSS in most advanced lesions (those with plaque burden [PB]>60%). The change in PSS was both dependent on drug therapy and baseline disease severity, and the protective effect of HIS seemed to be mediated by remodelling plaque microstructure and lumen surface. Second, it shows that plaque geometric parameters, especially the longitudinal variation measured by heterogeneity index of lumen roughness, curvature, and irregularity, can identify plaques that subsequently developed adverse clinical events. Lumen roughness heterogeneity showed a weak correlation with PSS and was an independent predictor of adverse clinical events. Finally, the role of combined PSS and ESS in plaque risk prediction was assessed through a subgroup analysis of the PROSPECT (A Prospective Natural-History Study of Coronary Atherosclerosis) study, with results suggesting that incorporation of ESS, ESS gradient, and PSS heterogeneity can improve the capability of VH-IVUS to identify plaques that lead to such events.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Gu, Zhaotao Sophie

Advisor dc:contributor.advisor

• Bennett, Martin

• atherosclerosis
• biomechanics
• intracoronary imaging
• adverse clinical events
• pharmacotherapy

Licence

• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.93249

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/345827